PD-1: A Negative Regulator of Phagocytosis by Tumour-Associated Macrophages in Colon Cancer

ABSTRACT

Programmed cell death protein 1 (PD-1) is an immuno-inhibitory cell surface receptor protein of the myeloid, and lymphoid cell. PD-L1 is the ligand of PD-1, which is abundant in different malignant tissue e.g. skin, colon and breast cancer. PD-1/PD-L1 interaction helps the tumour cell to escape from the immune response by limiting TCR mediated T lymphocytes proliferation. Recently, PD-1 or PD-L1 blocking immunotherapy proved their efficacy in the treatment of different cancers. However, PD-1/PD-L1 interaction is well studied in T lymphocytes, but little is known about its function in tumour-associated macrophages (TAMs). In the tumour microenvironment, phagocytosis by TAMs plays a vital role in the immune response. In this review, the significance of PD-1 expression by TAMs and how it influences tumour immunity will be discussed. Recently, it has been found that PD-1 can express by TAMs and its expression level is directly related to duration and stages of colon cancer. TAMs expression of PD-1 was shown to be related to significant depletion of cancer cell phagocytosis. Monoclonal antibody against either PD-1 or PD-L1 in mice model of colon cancer promotes tumour cell phagocytosis by TAMs, thereby limiting the growth of the tumour and increase life expectancy. Therefore, PD-1 can be a promising target in macrophage-mediated immune therapy.