Trial Watch: Immunotherapy plus radiation therapy for oncological indications

ABSTRACT Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation.

[1]  E. Giannoni,et al.  Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts , 2014, Oncotarget.

[2]  Joe Y. Chang,et al.  Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? , 2016, Nature Reviews Clinical Oncology.

[3]  A. Santoro,et al.  Trabectedin for the treatment of soft tissue sarcomas , 2016, Expert opinion on pharmacotherapy.

[4]  A. Jemal,et al.  Cancer treatment and survivorship statistics, 2016 , 2016, CA: a cancer journal for clinicians.

[5]  K. Sankhala,et al.  Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives , 2016, Advances in Therapy.

[6]  Y. Yamada,et al.  Non-randomized phase II study to assess the efficacy of pembrolizumab (Pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients. , 2016 .

[7]  Melissa L. Johnson,et al.  A first-in-human study of REGN2810, a monoclonal, fully human antibody to programmed death-1 (PD-1), in combination with immunomodulators including hypofractionated radiotherapy (hfRT). , 2016 .

[8]  A. Tosti,et al.  Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells , 2016, Haematologica.

[9]  S. Reed,et al.  Perioperative treatment with the new synthetic TLR‐4 agonist GLA‐SE reduces cancer metastasis without adverse effects , 2016, International journal of cancer.

[10]  Mechthild Krause,et al.  Radiation oncology in the era of precision medicine , 2016, Nature Reviews Cancer.

[11]  L. Zitvogel,et al.  Trial Watch—Small molecules targeting the immunological tumor microenvironment for cancer therapy , 2016, Oncoimmunology.

[12]  T. Lawrence,et al.  FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4. , 2016, Molecular cell.

[13]  J. Reichert Antibodies to watch in 2016 , 2016, mAbs.

[14]  L. Zitvogel,et al.  Trial Watch—Oncolytic viruses and cancer therapy , 2016, Oncoimmunology.

[15]  G. Lucignani,et al.  Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy , 2016, PloS one.

[16]  Adam D. Thomas,et al.  DNA damage and the balance between survival and death in cancer biology , 2015, Nature Reviews Cancer.

[17]  Michael Frankfurter,et al.  Cancer Principles Practice Of Oncology , 2016 .

[18]  R. Fietkau,et al.  Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors , 2016, Cancer Immunology, Immunotherapy.

[19]  S. Demaria,et al.  In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. , 2015, Vaccine.

[20]  L. Zitvogel,et al.  Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. , 2015, Cancer cell.

[21]  O. Garaschuk,et al.  Brain tumour cells interconnect to a functional and resistant network , 2015, Nature.

[22]  S. Demaria,et al.  Role of Local Radiation Therapy in Cancer Immunotherapy. , 2015, JAMA oncology.

[23]  F. Hamdy,et al.  Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair , 2015, Science Translational Medicine.

[24]  T. Conrads,et al.  The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo , 2015, Oncotarget.

[25]  S. Scarpace Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies , 2015, Drugs in context.

[26]  Jeong-Seok Nam,et al.  Combinatorial TGF-β attenuation with paclitaxel inhibits the epithelial-to-mesenchymal transition and breast cancer stem-like cells , 2015, Oncotarget.

[27]  C. Drake,et al.  Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. , 2015, The Lancet. Oncology.

[28]  E. Garon Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. , 2015, Seminars in oncology.

[29]  W. McBride,et al.  Opportunities and challenges of radiotherapy for treating cancer , 2015, Nature Reviews Clinical Oncology.

[30]  R. Korn,et al.  Safety and activity of RRx-001 in patients with advanced cancer: a first-in-human, open-label, dose-escalation phase 1 study. , 2015, The Lancet. Oncology.

[31]  M. Bylesjo,et al.  Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab , 2015, Journal of Immunotherapy for Cancer.

[32]  A. Zhavoronkov,et al.  Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation , 2015, Oncotarget.

[33]  K. Kehn-Hall,et al.  Mutation of the BRCA1 SQ-cluster results in aberrant mitosis, reduced homologous recombination, and a compensatory increase in non-homologous end joining , 2015, Oncotarget.

[34]  D. Ding,et al.  Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages , 2015, Oncotarget.

[35]  S. Demaria,et al.  Abstract 2493: Fractionated but not single dose radiation is an optimal adjuvant for in situ tumor vaccination , 2015 .

[36]  S. Demaria,et al.  Abstract 244: Abscopal responses in patients with refractory metastatic NSCLC treated with concurrent radiotherapy and CTLA-4 immune checkpoint blockade: evidence for the in situ vaccination hypothesis of radiotherapy , 2015 .

[37]  Axel Hoos,et al.  Big opportunities for small molecules in immuno-oncology , 2015, Nature Reviews Drug Discovery.

[38]  Jiang Li,et al.  COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells , 2015, Oncoimmunology.

[39]  S. Demaria,et al.  Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. , 2015, The Lancet. Oncology.

[40]  E. Yonemochi,et al.  Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin. , 2015, International journal of oncology.

[41]  A. Palamara,et al.  Historical review on thymosin α1 in oncology: preclinical and clinical experiences , 2015, Expert opinion on biological therapy.

[42]  J. Larkin,et al.  Pembrolizumab versus Ipilimumab in Advanced Melanoma. , 2015, The New England journal of medicine.

[43]  K. Nakayama,et al.  Fbxw7 suppresses cancer metastasis by inhibiting niche formation , 2015, Oncoimmunology.

[44]  L. Galluzzi,et al.  Combinatorial immunotherapy with checkpoint blockers solves the problem of metastatic melanoma—An exclamation sign with a question mark , 2015, Oncoimmunology.

[45]  M. Postow,et al.  Immune checkpoint modulation: rational design of combination strategies. , 2015, Pharmacology & therapeutics.

[46]  R. Stewart,et al.  PD-L1 blockade for cancer treatment: MEDI4736. , 2015, Seminars in oncology.

[47]  L. Zitvogel,et al.  Type I interferons in anticancer immunity , 2015, Nature Reviews Immunology.

[48]  J. Zavadil,et al.  TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity. , 2015, Cancer research.

[49]  H. Moch,et al.  Interaction of tumor cells with infiltrating lymphocytes via CD70 and CD27 in clear cell renal cell carcinoma , 2015, Oncoimmunology.

[50]  Troy Guthrie,et al.  Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  E. Celis,et al.  An optimized peptide vaccine strategy capable of inducing multivalent CD8+ T cell responses with potent antitumor effects , 2015, Oncoimmunology.

[52]  A. Jukkola-Vuorinen,et al.  Tumor infiltrating CD8+ T lymphocyte count is independent of tumor TLR9 status in treatment naïve triple negative breast cancer and renal cell carcinoma , 2015, Oncoimmunology.

[53]  M. Kortylewski,et al.  TLR9 signaling through NF-κB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells , 2015, Oncotarget.

[54]  R. Advani,et al.  Phase I/II study of intratumoral injection of SD-101, an immunostimulatory CpG, and intratumoral injection of ipillumumab, an anti-CTLA-4 monoclonal antibody, in combination with local radiation in low-grade B-cell lymphomas. , 2015 .

[55]  J. Lunceford,et al.  Pembrolizumab for the treatment of non-small-cell lung cancer. , 2015, The New England journal of medicine.

[56]  J. Schlom,et al.  Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti–PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells , 2015, Cancer Immunology Research.

[57]  L. Zitvogel,et al.  Trial Watch: Adoptive cell transfer for oncological indications , 2015, Oncoimmunology.

[58]  M. Okoniewski,et al.  Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. , 2015, Immunity.

[59]  E. Jaffee,et al.  Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  L. Zitvogel,et al.  Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications , 2015, Oncoimmunology.

[61]  T. Illidge,et al.  The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade , 2015, Oncoimmunology.

[62]  Annie A Wu,et al.  Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells , 2015, Oncoimmunology.

[63]  S. Mayor Radiation in combination with immune-checkpoint inhibitors. , 2015, The Lancet. Oncology.

[64]  N. Araki,et al.  Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. , 2015, The Lancet. Oncology.

[65]  C. Figdor,et al.  Intranodal vaccination with mRNA-optimized dendritic cells in metastatic melanoma patients , 2015, Oncoimmunology.

[66]  E. Tartour,et al.  Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer , 2015, Molecular Cancer Therapeutics.

[67]  J. Olweus,et al.  “In situ” vaccination for systemic effects in follicular lymphoma , 2015, Oncoimmunology.

[68]  N. Grishin,et al.  Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation , 2015, Science.

[69]  K. D. Castle,et al.  Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy , 2015, Science Translational Medicine.

[70]  M. Crittenden,et al.  Tumor immune remodeling by TGFβ inhibition improves the efficacy of radiation therapy , 2015, Oncoimmunology.

[71]  L. Galluzzi,et al.  Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin's lymphoma , 2015, Oncoimmunology.

[72]  Junnian Zheng,et al.  Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death. , 2015, Molecular medicine reports.

[73]  H. Ishwaran,et al.  Radiation and Dual Checkpoint Blockade Activates Non-Redundant Immune Mechanisms in Cancer , 2015, Nature.

[74]  P. Ott,et al.  PD-1 pathway inhibitors: The next generation of immunotherapy for advanced melanoma , 2015, Oncotarget.

[75]  S. Majumdar,et al.  The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ , 2015, Oncoimmunology.

[76]  Stephen J. Elledge,et al.  Homologous recombination-deficient tumors are hyper-dependent on POLQ-mediated repair , 2015, Nature.

[77]  M. Millenson,et al.  PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. , 2015, The New England journal of medicine.

[78]  D. Schadendorf,et al.  Nivolumab in previously untreated melanoma without BRAF mutation. , 2015, The New England journal of medicine.

[79]  A. Prica,et al.  Myelodysplastic syndrome successfully treated with adalimumab. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  L. Zitvogel,et al.  Trial Watch: Peptide-based anticancer vaccines , 2015, Oncoimmunology.

[81]  I. Svane,et al.  Indoleamine 2,3-dioxygenase vaccination , 2015, Oncoimmunology.

[82]  H. Kohrt,et al.  Trial watch: Tumor-targeting monoclonal antibodies for oncological indications , 2015, Oncoimmunology.

[83]  E. Jaffee,et al.  PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors , 2015, Journal of immunotherapy.

[84]  E. Gazzano,et al.  Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma , 2014, Oncotarget.

[85]  D Andrews,et al.  Essential versus accessory aspects of cell death: recommendations of the NCCD 2015 , 2014, Cell Death and Differentiation.

[86]  V. Devita,et al.  Comprar Cancer: Principles & Practice of Oncology, 2ª Ed. Primer Of The Molecular Biology Of Cancer | Vincent T. DeVita Jr. | 9781496310637 | Lippincott Williams & Wilkins , 2015 .

[87]  M. Foiani,et al.  Nuclear envelope and chromatin, lock and key of genome integrity. , 2015, International review of cell and molecular biology.

[88]  Yanfang Jiang,et al.  NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease. , 2015, International immunopharmacology.

[89]  D. Cimini,et al.  Link between aneuploidy and chromosome instability. , 2015, International review of cell and molecular biology.

[90]  More Benefits for Checkpoint Inhibitors in NSCLC. , 2015, Cancer Discovery.

[91]  H. Kohrt,et al.  Current clinical trials testing combinations of immunotherapy and radiation. , 2015, Seminars in radiation oncology.

[92]  S. Siva,et al.  Abscopal effects of radiation therapy: a clinical review for the radiobiologist. , 2015, Cancer letters.

[93]  G. Cheng,et al.  Radiation and inflammation. , 2015, Seminars in radiation oncology.

[94]  V. Brower New approaches tackle rising pancreatic cancer rates. , 2014, Journal of the National Cancer Institute.

[95]  Axel Hoos,et al.  Classification of current anticancer immunotherapies , 2014, Oncotarget.

[96]  R. Weichselbaum,et al.  STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. , 2014, Immunity.

[97]  L. Weiner,et al.  The development of immunoconjugates for targeted cancer therapy , 2014, Nature Reviews Clinical Oncology.

[98]  H. Ishwaran,et al.  Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways , 2014, Cell.

[99]  R. Emerson,et al.  PD-1 blockade induces responses by inhibiting adaptive immune resistance , 2014, Nature.

[100]  S. Demaria,et al.  Combinations of Immunotherapy and Radiation in Cancer Therapy , 2014, Front. Oncol..

[101]  L. Galluzzi,et al.  Impact of myeloid cells on the efficacy of anticancer chemotherapy. , 2014, Current opinion in immunology.

[102]  Antoni Ribas,et al.  Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial , 2014, The Lancet.

[103]  S. Tomida,et al.  Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions , 2014, Oncotarget.

[104]  C. Ries,et al.  Targeting tumor-associated macrophages in cancer therapy and understanding their complexity , 2014, Oncoimmunology.

[105]  L. Zitvogel,et al.  Trial Watch: Radioimmunotherapy for oncological indications , 2014, Oncoimmunology.

[106]  P. Vandenabeele,et al.  Consensus guidelines for the detection of immunogenic cell death , 2014, Oncoimmunology.

[107]  Kuender D Yang,et al.  Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation , 2014, Oncotarget.

[108]  B. Delahunt,et al.  Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. , 2014, The Lancet. Oncology.

[109]  L. Zitvogel,et al.  Trial watch: IDO inhibitors in cancer therapy , 2014, Oncoimmunology.

[110]  Jeong-Seok Nam,et al.  An novel inhibitor of TGF-β type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition. , 2014, Cancer letters.

[111]  Song Liu,et al.  FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics , 2014, Oncotarget.

[112]  Yanping Zhang,et al.  Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage. , 2014, Cancer cell.

[113]  L. Galluzzi,et al.  Organelle-specific initiation of cell death , 2014, Nature Cell Biology.

[114]  J. Gribben,et al.  Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy , 2014, Nature.

[115]  J. Joyce,et al.  Therapeutic targeting of tumor-associated macrophages and microglia in glioblastoma. , 2014, Immunotherapy.

[116]  P. A. Pérez-Mancera,et al.  Inside and out: the activities of senescence in cancer , 2014, Nature Reviews Cancer.

[117]  Jiang Li,et al.  Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma , 2014, Oncotarget.

[118]  S. Demaria,et al.  The Optimal Partnership of Radiation and Immunotherapy: from Preclinical Studies to Clinical Translation , 2014, Radiation research.

[119]  Wei Wang,et al.  Cytotoxic effect of a combination of bluetongue virus and radiation on prostate cancer , 2014, Experimental and therapeutic medicine.

[120]  R. Emerson,et al.  Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes , 2014, Oncoimmunology.

[121]  L. Chow,et al.  A new addition to the PD-1 checkpoint inhibitors for non-small cell lung cancer-the anti-PDL1 antibody-MEDI4736. , 2014, Translational Lung Cancer Research.

[122]  R. Weichselbaum,et al.  A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[123]  B. Tombal,et al.  Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. , 2014, The Lancet. Oncology.

[124]  L. Galluzzi,et al.  Systems biology of cisplatin resistance: past, present and future , 2014, Cell Death and Disease.

[125]  J. Banchereau,et al.  SnapShot: Cancer Vaccines , 2014, Cell.

[126]  A. Tutt,et al.  Immunological Visibility: Posttranscriptional Regulation of Human NKG2D Ligands by the EGF Receptor Pathway , 2014, Science Translational Medicine.

[127]  L. Wakefield,et al.  Synergistic antitumor effects of a TGFβ inhibitor and cyclophosphamide , 2014, Oncoimmunology.

[128]  S. Demaria,et al.  Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death , 2014, Oncoimmunology.

[129]  yang-xin fu,et al.  Radiation and anti-PD-L1 antibody combinatorial therapy induces T cell-mediated depletion of myeloid-derived suppressor cells and tumor regression , 2014, Oncoimmunology.

[130]  J. Galon,et al.  Imaging , Diagnosis , Prognosis Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer , 2014 .

[131]  Ya-jun Guo,et al.  Dual targeting of CD137 co-stimulatory and PD-1 co-inhibitory molecules for ovarian cancer immunotherapy , 2014, Oncoimmunology.

[132]  Roulstone,et al.  Synergistic cytotoxicity of radiation and oncolytic Lister strain vaccinia in V600D/EBRAF mutant melanoma depends on JNK and TNF-α signaling , 2014, Oncogene.

[133]  Zhiwei Wang,et al.  Aberrant regulation of FBW7 in cancer , 2014, Oncotarget.

[134]  J. Berzofsky,et al.  Phase I Study of GC1008 (Fresolimumab): A Human Anti-Transforming Growth Factor-Beta (TGFβ) Monoclonal Antibody in Patients with Advanced Malignant Melanoma or Renal Cell Carcinoma , 2014, PloS one.

[135]  G. Batist,et al.  Imiquimod in the treatment of breast cancer skin metastasis. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[136]  C. Zielinski A phase I study of MEDI4736, NNT-PD-L1 antibody in patients with advanced solid tumors. , 2014, Translational lung cancer research.

[137]  S. Formenti,et al.  Is tumor (R)ejection by the immune system the “5th R” of radiobiology? , 2014, Oncoimmunology.

[138]  V. Pant,et al.  Dissecting the p53-Mdm2 feedback loop in vivo: uncoupling the role in p53 stability and activity , 2014, Oncotarget.

[139]  R. Weichselbaum,et al.  Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. , 2014, The Journal of clinical investigation.

[140]  C. Pui,et al.  Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy , 2014, Health physics.

[141]  B. Ross,et al.  Mathematical Modeling of PDGF-Driven Glioblastoma Reveals Optimized Radiation Dosing Schedules , 2014, Cell.

[142]  D. Raulet,et al.  Immunosurveillance of senescent cancer cells by natural killer cells , 2014, Oncoimmunology.

[143]  M. Kortylewski,et al.  Push and release , 2014, Oncoimmunology.

[144]  T. Keler,et al.  Targeting human CD27 with an agonist antibody stimulates T-cell activation and antitumor immunity , 2014, Oncoimmunology.

[145]  F. Marincola,et al.  Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours , 2013, The Journal of pathology.

[146]  L. Zitvogel,et al.  Trial Watch , 2013, Oncoimmunology.

[147]  V. Bolanos-Garcia Formation of multiprotein assemblies in the nucleus: the spindle assembly checkpoint. , 2014, International review of cell and molecular biology.

[148]  J. Peterson,et al.  Cell and molecular biology of epidermal growth factor receptor. , 2014, International review of cell and molecular biology.

[149]  B. Creelan Update on immune checkpoint inhibitors in lung cancer. , 2014, Cancer control : journal of the Moffitt Cancer Center.

[150]  Yusuke Nakamura,et al.  Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients , 2014, Journal of Translational Medicine.

[151]  J. Stritzker,et al.  Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium , 2013, International journal of cancer.

[152]  K. Schäkel,et al.  Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy. , 2013, Cancer cell.

[153]  L. Vitale,et al.  Agonist Anti-Human CD27 Monoclonal Antibody Induces T Cell Activation and Tumor Immunity in Human CD27–Transgenic Mice , 2013, The Journal of Immunology.

[154]  Matthew G. Vander Heiden,et al.  Metabolic targets for cancer therapy , 2013, Nature Reviews Drug Discovery.

[155]  S. Demaria,et al.  An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer , 2013, Cancer Immunology Research.

[156]  S. Formenti,et al.  Changes in breast radiotherapy: prone positioning and hypofractionation. , 2013, Clinical journal of oncology nursing.

[157]  S. Demaria,et al.  The TLR7 agonist imiquimod as an adjuvant for radiotherapy-elicited in situ vaccination against breast cancer , 2013, Oncoimmunology.

[158]  R. Coler,et al.  MyD88 and TRIF synergistic interaction is required for TH1‐cell polarization with a synthetic TLR4 agonist adjuvant , 2013, European journal of immunology.

[159]  B. Baban,et al.  Cutting Edge: DNA Sensing via the STING Adaptor in Myeloid Dendritic Cells Induces Potent Tolerogenic Responses , 2013, The Journal of Immunology.

[160]  L. Zitvogel,et al.  Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. , 2013, Immunity.

[161]  Laurence Zitvogel,et al.  Trial Watch , 2013, Oncoimmunology.

[162]  J. Kopecka,et al.  Zoledronic Acid Restores Doxorubicin Chemosensitivity and Immunogenic Cell Death in Multidrug-Resistant Human Cancer Cells , 2013, PloS one.

[163]  L. Zitvogel,et al.  Trial Watch-Oncolytic viruses and cancer therapy. , 2016 .

[164]  Laurence Zitvogel,et al.  Immunogenic cell death in cancer therapy. , 2013, Annual review of immunology.

[165]  S. Demaria,et al.  Exploiting the stress response to radiation to sensitize poorly immunogenic tumors to anti-CTLA-4 treatment , 2013, Oncoimmunology.

[166]  S. Demaria,et al.  Combining radiotherapy and cancer immunotherapy: a paradigm shift. , 2013, Journal of the National Cancer Institute.

[167]  A. Chang,et al.  Effects of Tumor Irradiation on Host T-Regulatory Cells and Systemic Immunity in the Context of Adoptive T-Cell Therapy in Mice , 2013, Journal of immunotherapy.

[168]  F. Végran,et al.  Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth. , 2013, The Journal of investigative dermatology.

[169]  I. Stratford,et al.  Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma. , 2013, Blood.

[170]  Te Vuong,et al.  Past, present, and future of radiotherapy for the benefit of patients , 2013, Nature Reviews Clinical Oncology.

[171]  R. Coler,et al.  Cooperative intracellular interactions between MyD88 and TRIF are required for CD4 T cell T H 1 polarization with a synthetic TLR4 agonist adjuvant , 2013 .

[172]  Abhishek D. Garg,et al.  Immunogenic cell death and DAMPs in cancer therapy , 2012, Nature Reviews Cancer.

[173]  S. Demaria,et al.  Radiation therapy to convert the tumor into an in situ vaccine. , 2012, International journal of radiation oncology, biology, physics.

[174]  S. Demaria,et al.  Radiation as an immunological adjuvant: current evidence on dose and fractionation , 2012, Front. Oncol..

[175]  N. Kawashima,et al.  Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer , 2012, Clinical Cancer Research.

[176]  N. Kawashima,et al.  Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. , 2012, The Journal of clinical investigation.

[177]  S. Demaria,et al.  The convergence of radiation and immunogenic cell death signaling pathways , 2012, Front. Oncol..

[178]  A. Jemal,et al.  Cancer treatment and survivorship statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[179]  W. Urba,et al.  Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2—Tumor and Immunological Responses , 2012, Science Translational Medicine.

[180]  L. Galluzzi,et al.  Molecular mechanisms of cisplatin resistance , 2012, Oncogene.

[181]  Karolina Palucka,et al.  Cancer immunotherapy via dendritic cells , 2012, Nature Reviews Cancer.

[182]  A. Tefferi,et al.  Abscopal effect in a patient with melanoma. , 2012, New England Journal of Medicine.

[183]  J. Wolchok,et al.  Treatment of locally recurrent mucosal melanoma with topical imiquimod. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[184]  I. Navarro-Teulon,et al.  Clinical radioimmunotherapy—the role of radiobiology , 2011, Nature Reviews Clinical Oncology.

[185]  B. Hann,et al.  TGFβ1 Inhibition Increases the Radiosensitivity of Breast Cancer Cells In Vitro and Promotes Tumor Control by Radiation In Vivo , 2011, Clinical Cancer Research.

[186]  H. Nagawa,et al.  Intratumoral injection of interleukin‐2 augments the local and abscopal effects of radiotherapy in murine rectal cancer , 2011, Cancer science.

[187]  Lei Xu,et al.  Normalization of the vasculature for treatment of cancer and other diseases. , 2011, Physiological reviews.

[188]  L. Galluzzi,et al.  Mitotic catastrophe: a mechanism for avoiding genomic instability , 2011, Nature Reviews Molecular Cell Biology.

[189]  N. Aaronson,et al.  Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial. , 2011, Gynecologic oncology.

[190]  B. Lambrecht,et al.  Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. , 2011, Trends in immunology.

[191]  Stephanie Lamart,et al.  Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. , 2011, The Lancet. Oncology.

[192]  G. Remuzzi,et al.  A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis , 2011, Kidney international.

[193]  H. Ueno,et al.  Targeting human dendritic cell subsets for improved vaccines. , 2011, Seminars in immunology.

[194]  E. Tartour,et al.  Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy , 2011, Cancer and Metastasis Reviews.

[195]  Stephen L. Brown,et al.  Decreasing the Adverse Effects of Cancer Therapy: National Cancer Institute Guidance for the Clinical Development of Radiation Injury Mitigators , 2010, Clinical Cancer Research.

[196]  H. Ueno,et al.  The expanding family of dendritic cell subsets , 2010, Nature Biotechnology.

[197]  E. Yorke,et al.  Use of normal tissue complication probability models in the clinic. , 2010, International journal of radiation oncology, biology, physics.

[198]  N. Kawashima,et al.  Radiotherapy Enhances Antitumor Effect of Anti-CD137 Therapy in a Mouse Glioma Model , 2010, Radiation research.

[199]  S. Formenti Immunological aspects of local radiotherapy: clinical relevance. , 2010, Discovery medicine.

[200]  Hua Yu,et al.  In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses , 2009, Nature Biotechnology.

[201]  N. Kawashima,et al.  Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 Antibody , 2009, Clinical Cancer Research.

[202]  D. Raulet,et al.  Oncogenic stress sensed by the immune system: role of natural killer cell receptors , 2009, Nature Reviews Immunology.

[203]  Kevin M. Prise,et al.  Radiation-induced bystander signalling in cancer therapy , 2009, Nature Reviews Cancer.

[204]  Kun-Liang Guan,et al.  Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α , 2009, Science.

[205]  M. Tubiana Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[206]  Alison M. Dunning,et al.  Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype , 2009, Nature Reviews Cancer.

[207]  F. Ducray,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[208]  W. Gradishar,et al.  American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[209]  D. Raulet,et al.  Regulation of NK cell responsiveness to achieve self‐tolerance and maximal responses to diseased target cells , 2008, Immunological reviews.

[210]  N. Aaronson,et al.  Treatment of vulvar intraepithelial neoplasia with topical imiquimod. , 2008, The New England journal of medicine.

[211]  Arthur M. Krieg,et al.  Toll-like receptor 9 (TLR9) agonists in the treatment of cancer , 2008, Oncogene.

[212]  Jens Overgaard,et al.  Hypoxic radiosensitization: adored and ignored. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[213]  J. Campisi,et al.  Cellular senescence: when bad things happen to good cells , 2007, Nature Reviews Molecular Cell Biology.

[214]  Philippe Dessen,et al.  A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib. , 2007, Cancer research.

[215]  L. Constine,et al.  Normal tissue tolerance dose metrics for radiation therapy of major organs. , 2007, Seminars in radiation oncology.

[216]  Karen H. Vousden,et al.  p53 in health and disease , 2007, Nature Reviews Molecular Cell Biology.

[217]  Po-Huang Lee,et al.  Radiation-Induced Hepatitis B Virus Reactivation in Liver Mediated by the Bystander Effect from Irradiated Endothelial Cells , 2007, Clinical Cancer Research.

[218]  D. Brenner,et al.  Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[219]  Geoff Delaney,et al.  The role of radiotherapy in cancer treatment , 2005, Cancer.

[220]  Joseph M Kaminski,et al.  The controversial abscopal effect. , 2005, Cancer treatment reviews.

[221]  R. Jain Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[222]  E. Hall,et al.  Radiation oncology: a century of achievements , 2004, Nature Reviews Cancer.

[223]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[224]  N. Kawashima,et al.  Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. , 2004, International journal of radiation oncology, biology, physics.

[225]  C. Mothersill,et al.  Radiation-induced bystander effects — implications for cancer , 2004, Nature Reviews Cancer.

[226]  K. Prise,et al.  Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. , 2003, Cancer research.

[227]  C Norman Coleman,et al.  Effects of radiation on normal tissue: consequences and mechanisms. , 2003, The Lancet. Oncology.

[228]  C. N. Coleman,et al.  CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. , 2003, Seminars in radiation oncology.

[229]  E. Winer,et al.  2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[230]  R. Orecchia,et al.  Radiotherapy-related fatigue. , 2002, Critical reviews in oncology/hematology.

[231]  H. Matsumoto,et al.  Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells , 2002, International journal of radiation biology.

[232]  R. Miralbell,et al.  Total body irradiation before allogeneic bone marrow transplantation: is more dose better? , 2001, International journal of radiation oncology, biology, physics.

[233]  B. Vikram,et al.  Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[234]  B. Lehnert,et al.  Factors underlying the cell growth-related bystander responses to alpha particles. , 2000, Cancer research.

[235]  E H Goodwin,et al.  Alpha particles induce the production of interleukin-8 by human cells. , 1999, Radiation research.

[236]  E H Goodwin,et al.  Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. , 1997, Cancer research.

[237]  Stephen N. Jones,et al.  Regulation of p53 stability by Mdm2 , 1997, Nature.

[238]  M. Goitein,et al.  Tolerance of normal tissue to therapeutic irradiation. , 1991, International journal of radiation oncology, biology, physics.

[239]  M. Lederman Advances in radiotherapy. , 1970, The Practitioner.