Potential Targets for Pancreatic Cancer Immunotherapeutics

Abstract

Pancreatic adenocarcinoma is the fourth leading cause of cancer death with an overall 5-year survival of less than 5%. As there is ample evidence that pancreatic adenocarcinomas elicit antitumor immune responses, identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. While promising results have been observed in animal tumor models, most clinical studies have found only limited success. As most trials were performed in patients with advanced pancreatic cancer, the contribution of immune suppressor mechanisms should be taken into account. In this article, we detail recent work in tumor antigen vaccination and the recently identified mechanisms of immune suppression in pancreatic cancer. We offer our perspective on how to increase the clinical efficacy of vaccines for pancreatic cancer.

IP-10/CXCL10 attracts regulatory T cells: Implication for pancreatic cancer

“…Several clinical trials are implementing immunotherapy for the treatment of PDAC. 8 Two different approaches are currently being applied. CTLA4 and PD-1 blocking antibodies alone or in combination with chemo-or radiotherapy are being deployed to inhibit the immunosuppressive activity of Tregs against reactive T cells (NCT01313416, NCT0230518, NCT02303990, NCT00112580; www.…”

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

“…Immunotherapy is considered to be a fourth treatment procedure for cancer following surgical resection, radiotherapy, and chemotherapy [29]. Cancer vaccine therapy was previously shown to convey survival benefits to prostate cancer patients in a clinical phase III trial [30], and some candidates of other cancers have been identified Therapeutic function is the most important factor to consider when determining the usefulness of cancer antigens for peptide vaccine therapy.…”

Current concepts and novel targets in advanced pancreatic cancer

“…In contrast to targeted approaches that aim to inhibit molecular pathways crucial for tumour growth and maintenance, immunotherapy endeavours to stimulate a host immune response that results in long-term tumour destruction 67. The stroma of pancreatic cancer is particularly rich in inflammatory cells that are proposed to mediate drug resistance and tumour progression 68. Therefore, immune cells such as T cells and macrophages infiltrating the peritumoral stroma represent a promising target for immunotherapeutic approaches.…”