TY - JOUR
T1 - Is there an opportunity for current chemotherapeutics to up-regulate MIC-A/B ligands?
AU - Quirk, Kendel
AU - Ganapathy-Kanniappan, Shanmugasundaram
N1 - Publisher Copyright:
© 2017 Quirk and Ganapathy-Kanniappan.
PY - 2017/10/17
Y1 - 2017/10/17
N2 - 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 Perspective 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 Perspective is to underscore the prospects of current chemotherapeutics in NK cell immunotherapy, and discuss potential challenges and opportunities to improve cancer therapy.
AB - 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 Perspective 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 Perspective is to underscore the prospects of current chemotherapeutics in NK cell immunotherapy, and discuss potential challenges and opportunities to improve cancer therapy.
KW - Cancer
KW - Doxorubicin
KW - Immunotherapy
KW - MIC-A/B
KW - Natural killer cells
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UR - http://www.scopus.com/inward/citedby.url?scp=85031806944&partnerID=8YFLogxK
U2 - 10.3389/fphar.2017.00732
DO - 10.3389/fphar.2017.00732
M3 - Article
C2 - 29089892
AN - SCOPUS:85031806944
VL - 8
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - OCT
M1 - 732
ER -