Colorectal pair. PD-1 (CD 279) expressed on

Colorectal cancer (CRC) is one of the most important
neoplasms accompanied by high rate of morbidity and mortality and  the third most frequent cause of death in the
world (1). Some risk factors are  involved in CRC for example being older than
50, ulcerative colitis, smoking, alcohol, sedentary lifestyle but it can be
caused by some genetic  instabilities too,
including CIN (Chromosomal Instability ), MSI ( Micro Satellite Instability )
and CIMP ( CPG Islands Metilator Phenotypes ) (1). According to different causes, CRC can show various features and
phenotypes, therefore it needs different types of treatments or managements for
advanced forms and biomarkers to follow. However, by using a combination of chemotherapy
and biologic targets, taking into consideration their cytotoxic side effects,
overall survival of patients has increased to more than 2 years, median(2). So there is a real need for improving therapies and also growing
evidence on the role of immune system in occurrence, growth, development and metastasis
of tumors(3). In this scenario, focusing on immune checkpoint inhibitors in
cancer therapy may have promising outcomes.

Our immune system encounters tumor
cells through a combination of biological pathways. Opposing to the fact that
the immune system should reject cancer cells due to their unusual markers and
genetic profile, the predominant way of interaction is Tolerance, in which
cancer cells are recognized as self cells(4).Tolerance results from various mechanisms such as regulatory T
cell functions, immunosuppressive cytokines and chemokines like IL-10 and TGF-?
and immunologic checkpoint pathways that are responsible for down modulation of
immune responses. One of the most important immune checkpoints is the
programmed cell death protein 1(PD-1), PD-1 ligand 1(PD-L1) or (PD-L2) receptor
ligand pair.

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 PD-1 (CD 279) expressed on the cell surface of
T and B lymphocytes and NK cells, predominantly affect CD8+ T cells as the
first line of defense against tumor cells, thus its normal function is to keep
immune homeostasis in cancer cells leading to evading immune attack (5, 6). Monoclonal antibodies
against this checkpoint like nivolumab and pembrolizumab are FDA approved drugs
for tumor cells producing PD-L1 or PD-L2 as PD-1 ligand such as  advanced melanoma (31–44% of patients) (7-11),
non-small-cell lung cancer (NSCLC; 19–20%) (9, 12, 13) and
renal cell carcinoma (RCC; 22–25%) 

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