Another important step towards understanding tumor immune evasion—novel mechanisms of PD-L1 overexpression

Recent advancements in the search for new treatment strategies for cancer have led to the development of therapeutic agents that target specific molecules that are critical to cancer development and/or expansion. The inhibition of the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway is one of such upcoming strategies that is being extensively explored in the field of oncology. Immunotherapy agents targeting the PD-1/PD-L1 signaling pathway have demonstrated promising anti-tumor efficacy in several malignancies, including non-small cell lung cancer (NSCLC) and melanoma, among others (1-6). Tumor cells are known to overexpress PD-L1, which aids in immune evasion by inducing T cell anergy and exhaustion within the tumor microenvironment (7). Several chromosomal alterations, most notably 9p24.1 amplification [identified in Hodgkin’s lymphoma (HL) cell lines], are reported to result in overexpression of PD-1 ligands (8,9). In addition, endogenous molecules such as interferon-γ (IFNγ) have also been identified to induce PD-L1 overexpression (10,11). The ability of tumors to suppress the host immune response is considered to be central to the clinical benefit observed with immunotherapy agents targeting the PD-1/PD-L1 signaling pathway (8,12-17). The mechanistic relationship between evasion of endogenous immunity by cancer cells and overexpression of PD-1 ligands, however, is not fully understood.