The Role of Mucosal Associated Invariant t Lymphocytes in Breast Cancer

Evaluation of MAIT cells in patient recently diagnosed as cancer breast and its correlation with clinical outcome.

Mucosal Associated Invariant T cells are a population of unconventional T cells which are enriched in mucosal tissues such as the lung and gut but are also present in other tissues including the skin, adipose tissue and the liver [4,5,6,7]. Unlike conventional T cells, MAIT cells are not restricted by MHC but recognize the MHC-related protein MR1. MAIT cells express a semi-invariant TCR α-chain (Vα7.2-Jα33/20/12 in humans) and a limited repository of TCR-β chains, mostly from the TRBV20 and TRBV6 gene families [8,9]

MAIT cells can also be activated independent of TCR engagement, via pro-inflammatory cytokines such as IL-18 [10,11,12]. Upon activation, MAIT cells can rapidly respond, producing a milieu of cytokines including interferon-gamma , tumor necrosis factor alpha and interleukin-17 [11,14]. MAIT cell cytokine profiles can vary depending on their tissue localization [15].

Peripheral MAIT cells are potent producers of IFNγ and TNFα, whereas IL-17 producing MAIT cells are rare in the periphery but are more abundant in, for example, the female genital mucosa [16]. In addition to cytokine production, A central role in immune protection against cancer is played by T lymphocytes, particularly CD8+ T cells .Their infiltration in tumor cell nests is usually associated with a favorable prognosis and may predict outcome of therapies with drugs that block immune inhibitory receptors (checkpoint blockade.

A recent meta-analysis reported that tumor-infiltrating CD8+ lymphocytes can be identified in 48% of all breast cancers .Interestingly, triple-negative breast cancers show the highest incidence of lymphocyte predominance. Moreover, TILs were found to be prognostic in triple-negative breast cancer, and higher levels of TILs were predictive for trastuzumab benefit in HER2+ disease. These findings suggest that therapies that enforce immune responses could potentially improve patient survival.