4.6 Article

Immune checkpoint blockade in pancreatic cancer: Trudging through the immune desert

期刊

SEMINARS IN CANCER BIOLOGY
卷 86, 期 -, 页码 14-27

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2022.08.009

关键词

Pancreatic cancer; Immunotherapy; Immune checkpoint; Tumor microenvironment; Cancer-associated fibroblast; Regulation network; Cytokine; Combination therapy

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资金

  1. NIH [R01 CA273349, R01 CA263575, R01 CA256973, R01 CA254036, R01 CA247471, R01 CA210637, R01 CA206444, U01 CA200466, U01 CA210240, P01 CA217798, R44 CA235991, P30 CA036727, T32 CA009476, U54 GM115458]

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Pancreatic cancer has high mortality and limited response to immunotherapy due to the immuno-suppressive tumor microenvironment and high expression of immune checkpoints. Combining immunotherapy with modulators of the tumor microenvironment may lead to the development of new therapeutic regimens.
Pancreatic cancer (PC) has exceptionally high mortality due to ineffective treatment strategies. Immunotherapy, which mobilizes the immune system to fight against cancer, has been proven successful in multiple cancers; however, its application in PC has met with limited success. In this review, we articulated that the pancreatic tumor microenvironment is immuno-suppressive with extensive infiltration by M2-macrophages and myeloid-derived suppressive cells but low numbers of cytotoxic T-cells. In addition, low mutational load and poor an-tigen processing, presentation, and recognition contribute to the limited response to immunotherapy in PC. Immune checkpoints, the critical targets for immunotherapy, have high expression in PC and stromal cells, regulated by tumor microenvironmental milieu (cytokine and metabolites) and cell-intrinsic mechanisms (epigenetic regulation, oncogenic signaling, and post-translational modifications). Combining immunotherapy with modulators of the tumor microenvironment may facilitate the development of novel therapeutic regimens to manage PC.

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