Research progress on the intrinsic non‑immune function of PD‑L1 in tumors (Review)

Abstract

Programmed death ligand 1 (PD-L1) is widely expressed in human tumors. It is widely known for its immunosuppressive function as it can help tumor cells evade T cell immune killing through the PD-1/PD-L1 signal. A number of clinical trials have proved that the destruction of the combination of PD-1 and PD-L1 by antibodies could significantly affect patients with advanced cancer. However, a number of patients with cancer still cannot benefit from PD-1/PD-L1 blocking therapy. The main reason is that PD-L1 also has some intrinsic regulatory functions to promote the progression of tumors. PD-L1 Protein contains an intrinsic domain that could link to other signal pathways, but the mechanism has not yet been fully revealed. The present review mainly discussed the non-immune checkpoint functions of PD-L1, such as its role in regulating cell proliferation, cell metabolism, drug resistance and maintaining epithelial-mesenchymal transition and stemness. Contents 1. Introduction 2. Molecular structure of PD-L1 3. Expression of PD-L1 in cancer and its potential clinical relevance 4. Intrinsic non-immune function of PD-L1 5. Conclusions

PDL1 targeting by miR-138-5p amplifies anti-tumor immunity and Jurkat cells survival in non-small cell lung cancer

“…PD1(also known as CD279) is a transmembrane receptor and apoptosis-associated molecule 10 that was known as a negative regulator of immune response by studying Nishimura and colleagues on PD1-defective mice 11 and expressed in T cells in peripheral tissues. PD-L1 (also known as B7-H1 or CD274) is a member of the B7-H1 transmembrane receptor family encoded by the CD274 gene located on chromosome 9 in the human genome 12 , and it is generally expressed on many cell types like T cells, B cells, and epithelial cells after stimulation and activation by pro-inflammatory cytokines like IFN-γ and IL4 13 .…”

Paving Way for a Paradigm Shift in Oncology: Curing Cancer by Loving It?

“…With the constant accrual of reports confirming the role of the cancer microenvironment in the tumor development, this physiological surrounding of the tumor, rather than the tumor per se, has started to be seen as the region where the therapeutic effect is ideally to be delivered. The major practical corollary of this new paradigm is that the treatment of cancer at the cellular scale need not target cancer cells per se, but can also focus on instructing their normal cellular neighbors on how to eradicate the tumor, as through vaccines [23], chimeric antigen receptor (CAR) T-cell therapies [24] or programmed death-ligand 1 (PD-L1) checkpoint inhibitor therapies [25] among others. In general, this has solidified immunotherapy as a major new direction in the treatment of cancer.…”