Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy

J Exp Clin Cancer Res. 2022 Feb 9;41(1):56. doi: 10.1186/s13046-022-02273-w.

Abstract

Mortality associated with pancreatic cancer is among the highest of all malignancies, with a 5-year overall survival of 5-10%. Immunotherapy, represented by the blocking antibodies against programmed cell death protein 1 or its ligand 1 (anti-PD-(L)1), has achieved remarkable success in a number of malignancies. However, due to the immune-suppressive tumor microenvironment, the therapeutic efficacy of anti-PD-(L)1 in pancreatic cancer is far from expectation. To address such a fundamental issue, chemotherapy, radiotherapy, targeted therapy and even immunotherapy itself, have individually been attempted to combine with anti-PD-(L)1 in preclinical and clinical investigation. This review, with a particular focus on pancreatic cancer therapy, collects current anti-PD-(L)1-based combination strategy, highlights potential adverse effects of accumulative combination, and further points out future direction in optimization of combination, including targeting post-translational modification of PD-(L)1 and improving precision of treatment.

Keywords: Combinational therapy; Immune checkpoint inhibitor; PD-1; PD-L1; Pancreatic cancer; Post-translational modification; Precision therapy; Systematic treatment.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / pharmacology
  • B7-H1 Antigen / therapeutic use*
  • Humans
  • Immunotherapy / methods*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Survival Analysis
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human