Tumor-intrinsic oncogene pathways mediating immune avoidance

ABSTRACT Immunotherapy is emerging as a major treatment for patients with cancer, predominantly via blocking immune inhibitory pathways and through adoptive T cell therapy. However, only a subset of patients shows clinical responses to these interventions. Emerging data indicates a correlation between clinical response and a pre-existing T cell-inflamed tumor microenvironment. Tumor-intrinsic β-catenin activation has been identified as mediating exclusion of T cells from the tumor microenvironment and other oncogene pathways are being explored similarly. Understanding the molecular mechanisms underlying immune avoidance should identify new therapeutic targets for expanding efficacy of immunotherapies.

[1]  K. Odunsi,et al.  Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints , 2015, Nature Communications.

[2]  J. Luke,et al.  Density of immunogenic antigens and presence or absence of the T cell-inflamed tumor microenvironment in metastatic melanoma. , 2015 .

[3]  George E. Katibah,et al.  Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity. , 2015, Cell reports.

[4]  T. Gajewski,et al.  Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity , 2015, Nature.

[5]  Martin L. Miller,et al.  Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer , 2015, Science.

[6]  T. Schumacher,et al.  Neoantigens in cancer immunotherapy , 2015, Science.

[7]  Benjamin Haibe-Kains,et al.  APOBEC3B expression in breast cancer reflects cellular proliferation, while a deletion polymorphism is associated with immune activation , 2015, Proceedings of the National Academy of Sciences.

[8]  P. Murray,et al.  Understanding Local Macrophage Phenotypes In Disease: Modulating macrophage function to treat cancer , 2015, Nature Medicine.

[9]  M. Vetizou,et al.  Cancer and the gut microbiota: An unexpected link , 2015, Science Translational Medicine.

[10]  J. Wolchok,et al.  Genetic basis for clinical response to CTLA-4 blockade in melanoma. , 2014, The New England journal of medicine.

[11]  Ying Wang,et al.  STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. , 2014, Immunity.

[12]  Charles J. Vaske,et al.  Lymphocyte Invasion in IC10/Basal-Like Breast Tumors Is Associated with Wild-Type TP53 , 2014, Molecular Cancer Research.

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

[14]  P. Pandolfi,et al.  Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. , 2014, Cell reports.

[15]  H. Koblish,et al.  Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8+ T cells directly within the tumor microenvironment , 2014, Journal of Immunotherapy for Cancer.

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

[17]  C. Slingluff,et al.  T cells in the human metastatic melanoma microenvironment express site‐specific homing receptors and retention integrins , 2014, International journal of cancer.

[18]  P. Sharma,et al.  PD-L1 Expression in Triple-Negative Breast Cancer , 2014, Cancer Immunology Research.

[19]  S. Lowe,et al.  p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells , 2013, The Journal of experimental medicine.

[20]  H. Schreiber,et al.  Innate and adaptive immune cells in the tumor microenvironment , 2013, Nature Immunology.

[21]  Jason B. Williams,et al.  Up-Regulation of PD-L1, IDO, and Tregs in the Melanoma Tumor Microenvironment Is Driven by CD8+ T Cells , 2013, Science Translational Medicine.

[22]  R. Carvajal,et al.  Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy , 2013, Expert opinion on biological therapy.

[23]  J. Stagg,et al.  Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects , 2013, Therapeutic advances in medical oncology.

[24]  A. Palucka,et al.  Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet? , 2013, Science.

[25]  F. Marincola,et al.  IRF5 gene polymorphisms in melanoma , 2012, Journal of Translational Medicine.

[26]  H. Zeh,et al.  NF-κB hyperactivation in tumor tissues allows tumor-selective reprogramming of the chemokine microenvironment to enhance the recruitment of cytolytic T effector cells. , 2012, Cancer research.

[27]  F. Marincola,et al.  A genetic inference on cancer immune responsiveness , 2012, Oncoimmunology.

[28]  David C. Smith,et al.  Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. , 2012, The New England journal of medicine.

[29]  Kenji Mizuguchi,et al.  Inhibitory roles of signal transducer and activator of transcription 3 in antitumor immunity during carcinogen-induced lung tumorigenesis. , 2012, Cancer research.

[30]  Mikala Egeblad,et al.  Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. , 2012, Cancer cell.

[31]  C. Slingluff,et al.  Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. , 2012, Cancer research.

[32]  A. Baldwin.  Regulation of cell death and autophagy by IKK and NF‐κB: critical mechanisms in immune function and cancer , 2012, Immunological reviews.

[33]  D. Rimm,et al.  β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. , 2011, Cancer cell.

[34]  K. Murphy,et al.  Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells , 2011, The Journal of experimental medicine.

[35]  P. Foubert,et al.  Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression. , 2011, Cancer cell.

[36]  D. Schadendorf,et al.  Improved survival with ipilimumab in patients with metastatic melanoma. , 2010, The New England journal of medicine.

[37]  T. Gajewski,et al.  Gene Signature in Melanoma Associated With Clinical Activity: A Potential Clue to Unlock Cancer Immunotherapy , 2010, Cancer journal.

[38]  K. Murphy,et al.  Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells , 2010, The Journal of experimental medicine.

[39]  M. Tretiakova,et al.  Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. , 2009, Cancer research.

[40]  R. DePinho,et al.  BRafV600E cooperates with Pten silencing to elicit metastatic melanoma , 2009, Nature Genetics.

[41]  T. Jacks,et al.  Regulated expression of a tumor-associated antigen reveals multiple levels of T-cell tolerance in a mouse model of lung cancer. , 2008, Cancer research.

[42]  Carlos Cordon-Cardo,et al.  Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas , 2007, Nature.

[43]  A. Baldwin,et al.  Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression , 2006, Oncogene.

[44]  L. Chin,et al.  Characterization of melanocyte‐specific inducible Cre recombinase transgenic mice , 2006, Genesis.

[45]  Hua Yu,et al.  Stat3 Activity in Melanoma Cells Affects Migration of Immune Effector Cells and Nitric Oxide-Mediated Antitumor Effects1 , 2005, The Journal of Immunology.

[46]  R. Würzner,et al.  Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8+ T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons , 2005, Journal of Virology.

[47]  Y. Ben-Neriah,et al.  NF-κB functions as a tumour promoter in inflammation-associated cancer , 2004, Nature.

[48]  R. Schreiber,et al.  Cancer immunoediting: from immunosurveillance to tumor escape , 2002, Nature Immunology.

[49]  U. Sinha,et al.  Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer—review of current data. , 2015, Oral oncology.

[50]  Hua Yu,et al.  Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells , 2004, Nature Medicine.

[51]  Rinat Abramovitch,et al.  NF-kappaB functions as a tumour promoter in inflammation-associated cancer. , 2004, Nature.