Immune-Checkpoint Molecules
Immune-checkpoint molecules such as programmed cell death 1 (PD-1), its ligand (PD-L1), T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), and cytotoxic T lymphocyte antigen 4 (CTLA-4) are also targets in advanced/metastatic NSCLC.29-31
PD-1/PD-L1
Elevated expression of PD-1 appears to play an inhibitory role in anti-tumor immunity and functions as a "brake" or "stop signal" of T-cell activation, allowing cancer cells to avoid the immune response. Elevated levels of PD-L1 expression have been associated with increased tumor proliferation and aggressiveness. PD‑L1 is found on the surface of various cells, including macrophages, antigen-presenting cells, B and T lymphocytes, epithelial, muscle, and endothelial cells.29,32,33
TIGIT
There is in vitro evidence that TIGIT plays an important role in limiting adaptive and innate immunity against tumors. Its putative function is mediating recognition of self by natural killer (NK) cells, thus preventing killing of self-normal cells. TIGIT is found on the surfaces of NK cells, NK T cells, CD8+ T cells, CD4+ T cells, regulatory T cells, and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment.30,34,35
CTLA-4
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a receptor protein widely expressed on the surface of T and B lymphocytes and fibroblasts. Blocking the interaction between CTLA-4 and its ligand can help immune cells clear tumors via innate and adaptive immunity.31
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