Int J Biol Sci 2021; 17(10):2537-2547. doi:10.7150/ijbs.60114 This issue


New insights into the important roles of tumor cell-intrinsic PD-1

Hongmei Zheng, Yue Ning, Yuting Zhan, Sile Liu, Qiuyuan Wen, Songqing Fan

Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

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Zheng H, Ning Y, Zhan Y, Liu S, Wen Q, Fan S. New insights into the important roles of tumor cell-intrinsic PD-1. Int J Biol Sci 2021; 17(10):2537-2547. doi:10.7150/ijbs.60114. Available from

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Graphic abstract

PD-1 (Programmed cell death protein-1) is mainly expressed in various immune cells, while its ligands PD-L1/PD-L2 (Programmed death ligand-1/Programmed death ligand-2) are mostly expressed in tumor cells. Generally, the binding of PD-L1/PD-L2 and PD-1 could lead to the tumor immune evasion. However, some recent studies showed that PD-1 could also be expressed in tumor cells and could activate mTOR (Mammalian Target of Rapamycin) or Hippo signaling pathway, therefore facilitating tumor proliferation independent of the immune system. While there was evidence that tumor cell-intrinsic PD-1 inhibited the activation of AKT and ERK1/2 pathways, thereby inhibiting tumor cell growth. Based on TCGA and CCLE database, we found that PD-1 was expressed in a variety of tumors and was associated with patient's prognosis. Besides, we found that PD-1 may be involved in many carcinogenic signaling pathway on the basis of PD-1 gene enrichment analysis of cancer tissues and cancer cells. Our understanding of the tumor cell-intrinsic PD-1 function is still limited. This review is aimed at elaborating the potential effects of tumor cell-intrinsic PD-1 on carcinogenesis, providing a novel insight into the effects of anti-PD-1/PD-L1 immunotherapy, and helping to open a major epoch of combination therapy.

Keywords: PD-L1, tumor cell-intrinsic PD-1, immunotherapy