PD‐1/PD‐L1 pathway: Basic biology and role in cancer immunotherapy

Abstract

Over the course of past few years, cancer immunotherapy has been accompanied with promising results. However, preliminary investigations with respect to immunotherapy concentrated mostly on targeting the immune checkpoints, nowadays, emerge as the most efficient strategy to raise beneficial antitumor immune responses. Programmed cell death protein 1 (PD‐1) plays an important role in subsiding immune responses and promoting self‐tolerance through suppressing the activity of T cells and promoting differentiation of regulatory T cells. PD‐1 is considered as an immune checkpoint and protects against autoimmune responses through both induction of apoptosis in antigen‐specific T cells and inhibiting apoptosis in regulatory T cells. Several clinical trials exerting PD‐1 monoclonal antibodies as well as other immune‐checkpoint blockades have had prosperous outcomes and opened new horizons in tumor immunotherapy. Nonetheless, a bulk of patients have failed to respond to these newly emerging immune‐based approach and the survival rate was not satisfying. Additional strategies, especially combination therapies, has been initiated and been further promising. Attempts to identify novel and well‐suited predictive biomarkers are also sensed. In this review, the promotion of cancer immunotherapy targeting PD‐1 immunoinhibitory pathway is discussed.

Correlations of PD-1/PD-L1 Gene Polymorphisms with Susceptibility and Prognosis in Non-Hodgkin lymphoma in Iranian Population

“…Cancer cells can activate a variety of immune checkpoint pathways such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) to induce immunosuppressive functions. The PD-1/PD-L1 signaling pathway plays an important role in immune tolerance and prevention of autoimmune disorders (2). PD-1 is mainly expressed on the surface of activated immune cells such as T cells, natural killer cells, B cells, macrophages, and dendritic cells (3).…”

The Emerging Role of the c-MET-HGF Axis in Non-small Cell Lung Cancer Tumor Immunology and Immunotherapy

“…As a means of preventing excessive immune response in the face of chronic antigen stimulation T-cell activity can be suppressed by binding of PD-1 to ligands on dendritic cells, B-cells and macrophage and cancer cells such as PD-L1 which are increased by inflammation or by some cancer mutations (22). PD-L1 binding with PD-1 on activated T-lymphocytes inhibits Tcell proliferation and cytokine release (22)(23)(24), thus inhibiting anti-tumor immune responses. PD-L1 expression occurs more frequently with MET activation in NSCLC (25), suggesting that besides its well-characterized direct anti-tumor effects inhibition of c-MET signaling may act indirectly to alleviate immunosuppression.…”

A kinome‐wide screen using a NanoLuc LATS luminescent biosensor identifies ALK as a novel regulator of the Hippo pathway in tumorigenesis and immune evasion

“…We also show that YAP/TAZ are critical downstream genes mediating ALK‐induced increased cell proliferation and colony formation. Most recently, ALK was reported as a novel regulator of PD‐L1 (23, 24), a checkpoint gene that is overexpressed in various cancers enhancing their tumorigenic functions by either evading immune surveillance (immune evasion) via PD‐1–mediated T‐cell inactivation (41, 42) or activating the intrinsic oncogenic pathway (43, 44). In this study, we further show that YAP/TAZ are critical in mediating ALK‐induced up‐regulation of PD‐L1 in multiple cancer cell lines.…”