Spontaneous Regression of Ovarian Carcinoma After Septic Peritonitis; A Unique Case Report

Despite advances in therapy, ovarian cancer remains the most lethal gynecological malignancy and prognosis has not substantially improved over the past 3 decades. Immunotherapy is a promising new treatment option. However, the immunosuppressive cancer microenvironment must be overcome for immunotherapy to be successful. Here, we present a unique case of spontaneous regression of ovarian carcinoma after septic peritonitis. A 79-year-old woman was diagnosed with stage IIIc ovarian cancer. The omental cake biopsy was complicated by sepsis. Although the patient recovered, her physical condition did not allow further treatment for her ovarian cancer. After 6 months, spontaneous regression of the tumor was observed during surgery. Analysis of the immune infiltrate in the tissues showed a shift from a pro-tumorigenic to an anti-tumorigenic immune response after sepsis. Strong activation of the immune system during sepsis overruled the immunosuppressive tumor microenvironment and allowed for a potent anti-tumor immune response. More understanding of immunological responses in cases with cancer and septic peritonitis might be crucial to identify potential new targets for immunotherapy.

[1]  V. Badovinac,et al.  Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival , 2019, The Journal of Immunology.

[2]  Keunchil Park,et al.  Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. , 2018, The Lancet. Oncology.

[3]  B. Nelson,et al.  Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study , 2018, Oncoimmunology.

[4]  J. Vincent,et al.  Mechanisms and treatment of organ failure in sepsis , 2018, Nature Reviews Nephrology.

[5]  Brian J. Stevenson,et al.  Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer , 2018, Science Translational Medicine.

[6]  K. Kelly,et al.  Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials , 2018, Cancer.

[7]  D. Rimm,et al.  Exceptional response to pembrolizumab in a metastatic , chemotherapy / radiation-resistant ovarian 1 cancer patient harboring a PD-L 1-genetic rearrangement 2 , 2018 .

[8]  Inge M. N. Wortel,et al.  Eight-Color Multiplex Immunohistochemistry for Simultaneous Detection of Multiple Immune Checkpoint Molecules within the Tumor Microenvironment , 2018, The Journal of Immunology.

[9]  D. Matei,et al.  Pembrolizumab in patients (pts) with PD-L1–positive (PD-L1+) advanced ovarian cancer: Updated analysis of KEYNOTE-028. , 2017 .

[10]  M. Netea,et al.  The immunopathology of sepsis and potential therapeutic targets , 2017, Nature Reviews Immunology.

[11]  T. Randall,et al.  Ovarian cancer and the immune system - The role of targeted therapies. , 2016, Gynecologic oncology.

[12]  K. Kelly,et al.  Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity. , 2016 .

[13]  M. Morgan,et al.  Anti-mesothelin chimeric antigen receptor T cells in patients with epithelial ovarian cancer. , 2016 .

[14]  I. Christensen,et al.  Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma , 2015, Cancer Immunology, Immunotherapy.

[15]  K. Yamaguchi,et al.  Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  M. Donia,et al.  Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma , 2015, Human vaccines & immunotherapeutics.

[17]  R. Torensma,et al.  Cellular immunotherapy in ovarian cancer: Targeting the stem of recurrence. , 2015, Gynecologic oncology.

[18]  R. Hotchkiss,et al.  Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy , 2013, Nature Reviews Immunology.

[19]  R. Hotchkiss,et al.  The changing immune system in sepsis , 2013, Virulence.

[20]  Drew A. Torigian,et al.  A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside , 2013, Clinical Cancer Research.

[21]  M. Netea,et al.  Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? , 2013, American journal of respiratory and critical care medicine.

[22]  L. Zitvogel,et al.  OncoImmunology: a new journal at the frontier between oncology and immunology , 2012, Oncoimmunology.

[23]  J. A. Thomas,et al.  The role of innate immunity in spontaneous regression of cancer. , 2011, Indian journal of cancer.

[24]  C. Figdor,et al.  Ovarian cancer creates a suppressive microenvironment to escape immune elimination. , 2010, Gynecologic oncology.

[25]  T. Whiteside,et al.  TLR4 signaling induced by lipopolysacharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer , 2009, Oncogene.

[26]  P. Allavena,et al.  Macrophage polarization in tumour progression. , 2008, Seminars in cancer biology.

[27]  T. Whiteside,et al.  Toll-like receptor 4 (TLR4) promotes survival of ovarian cancer cells through induction of cell proliferation and apoptosis resistance , 2008 .

[28]  S. Rosenberg,et al.  Adoptive cell transfer: a clinical path to effective cancer immunotherapy , 2008, Nature Reviews Cancer.

[29]  S. Rosenberg,et al.  Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes , 2006, Science.

[30]  C. Figdor,et al.  Targeting antigens to dendritic cells in vivo. , 2006, Immunobiology.

[31]  George Coukos,et al.  Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival , 2004, Nature Medicine.

[32]  R. Hotchkiss,et al.  The pathophysiology and treatment of sepsis. , 2003, The New England journal of medicine.

[33]  P. Allavena,et al.  Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. , 2002, Trends in immunology.

[34]  W. Jonas,et al.  Fever, Cancer Incidence and Spontaneous Remissions , 2001, Neuroimmunomodulation.

[35]  S. Rosenberg,et al.  A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. , 1986, Science.

[36]  G QVIST,et al.  Spontaneous Regression of Cancer , 1963, British medical journal.

[37]  T. Jessy.  Immunity over inability: The spontaneous regression of cancer , 2011, Journal of natural science, biology, and medicine.

[38]  U. Hobohm,et al.  Pathogen-associated molecular pattern in cancer immunotherapy. , 2008, Critical reviews in immunology.

[39]  L. Trümper.  From bench to bedside , 2005, Medizinische Klinik.