AUTHOR=Quirk Kendel , Ganapathy-Kanniappan Shanmugasundaram 

TITLE=Is There an Opportunity for Current Chemotherapeutics to Up-regulate MIC-A/B Ligands?

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00732

DOI=10.3389/fphar.2017.00732

ISSN=1663-9812

ABSTRACT=<p>Natural killer (NK) cells are critical effectors of the immune system. NK cells recognize unhealthy cells by specific ligands [e.g., MHC- class I chain related protein A or B (MIC-A/B)] for further elimination by cytotoxicity. Paradoxically, cancer cells down-regulate MIC-A/B and evade NK cell’s anticancer activity. Recent data indicate that cellular-stress induces MIC-A/B, leading to enhanced sensitivity of cancer cells to NK cell-mediated cytotoxicity. In this <italic>Perspective</italic> article, we hypothesize that current chemotherapeutics at sub-lethal, non-toxic dose may promote cellular-stress and up-regulate the expression of MIC-A/B ligands to augment cancer’s sensitivity to NK cell-mediated cytotoxicity. Preliminary data from two human breast cancer cell lines, MDA-MB-231 and T47D treated with clinically relevant therapeutics such as doxorubicin, paclitaxel and methotrexate support the hypothesis. The goal of this <italic>Perspective</italic> is to underscore the prospects of current chemotherapeutics in NK cell immunotherapy, and discuss potential challenges and opportunities to improve cancer therapy.</p>