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MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity


Autoři: Mark Yarchoan aff001;  Aditya A. Mohan aff001;  Lauren Dennison aff001;  Teena Vithayathil aff001;  Amanda Ruggieri aff002;  Gregory B. Lesinski aff002;  Todd D. Armstrong aff001;  Nilofer S. Azad aff001;  Elizabeth M. Jaffee aff001
Působiště autorů: Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America aff001;  Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224600

Souhrn

Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined with systemic immunotherapies in preclinical models of RAS-driven tumors. MEK inhibitors have been shown to potentiate anti-tumor T cell immunity, but little is known about the effects of MEK inhibition on other immune subsets, including B cells. We show here that treatment with a MEK inhibitor reduces B regulatory cells (Bregs) in vitro, and reduces the number of Bregs in tumor draining lymph nodes in a colorectal cancer model in vivo. MEK inhibition does not impede anti-tumor humoral immunity, and B cells contribute meaningfully to anti-tumor immunity in the context of MEK inhibitor therapy. Treatment with a MEK inhibitor is associated with improved T cell infiltration and an enhanced response to anti-PD1 immunotherapy. Together these data indicate that MEK inhibition may reduce Bregs while sparing anti-tumor B cell function, resulting in enhanced anti-tumor immunity.

Klíčová slova:

B cells – Cancer immunotherapy – Cancer treatment – Cytotoxic T cells – Immune response – Lymph nodes – MAPK signaling cascades – T cells


Zdroje

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