Emerging trends in the immunotherapy of pancreatic cancer

• Published in: Cancer letters 2018-03, Vol.417, p.35-46
• Main Authors: Banerjee, Kasturi, Kumar, Sushil, Ross, Kathleen A., Gautam, Shailendra, Poelaert, Brittany, Nasser, Mohd Wasim, Aithal, Abhijit, Bhatia, Rakesh, Wannemuehler, Michael J., Narasimhan, Balaji, Solheim, Joyce C., Batra, Surinder K., Jain, Maneesh
• Format: Article
• Language: English
• Subjects: Animals; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Antigens, Neoplasm - therapeutic use; Autoantigens; Cancer therapies; Cancer vaccines; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Chemotherapy; Clinical trials; Cytotoxicity; Humans; Immune response; Immune system; Immunoglobulins; Immunological tolerance; Immunosuppression; Immunosurveillance; Immunotherapy; Immunotherapy - methods; Immunotherapy - trends; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Monoclonal antibodies; Pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - therapy; PD-L1; Signal transduction; Solid tumors; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tumor associated antigen; Tumor cells; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; Vaccines
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.12.012

Pancreatic cancer (PC) is the fourth leading cause of cancer-related deaths in the U.S., claiming approximately 43,000 lives every year. Much like other solid tumors, PC evades the host immune surveillance by manipulating immune cells to establish an immunosuppressive tumor microenvironment (TME). Therefore, targeting and reinstating the patient's immune system could serve as a powerful therapeutic tool. Indeed, immunotherapy has emerged in recent years as a potential adjunct treatment for solid tumors including PC. Immunotherapy modulates the host's immune response to tumor-associated antigens (TAAs), eradicates cancer cells by reducing host tolerance to TAAs and provides both short- and long-term protection against the disease. Passive immunotherapies like monoclonal antibodies or engineered T-cell based therapies directly target tumor cells by recognizing TAAs. Active immunotherapies, like cancer vaccines, on the other hand elicit a long-lasting immune response via activation of the patient's immune cells against cancer cells. Several immunotherapy strategies have been tested for anti-tumor responses alone and in combination with standard care in multiple preclinical and clinical studies. In this review, we discuss various immunotherapy strategies used currently and their efficacy in abrogating self-antigen tolerance and immunosuppression, as well as their ability to eradicate PC. •Pancreatic tumor microenvironment is immunosuppressive.•Targeting certain components of tumor microenvironment abrogates immunosuppression.•Several tumor-associated antigens have been evaluated for immunotherapy of PDAC.•Combination therapies involving checkpoint blockade agents have been promising.•Clinical & preclinical studies have identified challenges for immunotherapy of PDAC.