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

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.

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

“…The results shown that the PD-1 was high expression for pan-CK − cells in AAH/AIA stage, while inversely PD-1 was high expression for pan-CK + cells in MIA an IA stages. This is in line with a similar study showing that PD-1 could be expressed in tumor cells and could activate mTOR or Hippo signaling pathway, therefore facilitating tumor proliferation 59 . Taken together, interactions related to immunomodulatory signaling were more abundant in LUAD in comparison with normal, indicating heterogeneity and plasticity of the tumor ecosystem, varying during cancer progression.…”

Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

“…The discovery of tumor immune escape mechanisms promotes the development of immune checkpoint inhibitors (ICIs) [ 4 ]. However, non-sensitivity and adverse reactions to ICIs limited their practical application [ 5 , 6 ]. Therefore, there is a need to elucidate the mechanisms of cancer pathogenesis to predict and increase the sensitivity of ICIs for tumor patients.…”

Elevated PTTG1 predicts poor prognosis in kidney renal clear cell carcinoma and correlates with immunity

“…PD-1 inhibited the autoimmune response by binding PD-L1 or PD-L2 and inhibiting the function of T lymphocytes. Both PD-1 and PD-L1 have been found to be expressed in tumor cells, and the PD-1/PD-L2 axis has been shown to inhibit tumor growth via the AKT and ERK1/2 pathways [ 43 ]. CTLA-4 acted as a transmembrane receptor on T cells that bound to receptors on the surface of antigen cells to terminate the immune response [ 44 ].…”