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

Mark Yarchoan1, Aditya A Mohan1, Lauren Dennison1

  • 1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.

Plos One
|November 1, 2019
PubMed

Insights

Mitogen-activated protein kinase kinase (MEK) inhibitors reduce regulatory B cells (Bregs) in cancer models. This reduction spares anti-tumor B cell function, enhancing T cell infiltration and immunotherapy response.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Mitogen-activated protein kinase kinase (MEK) is a key target in RAS-driven cancers.
  • MEK inhibitors show promise when combined with immunotherapy, but their effects on B cells are unclear.

Purpose of the Study:

  • To investigate the impact of MEK inhibition on B cell subsets, particularly regulatory B cells (Bregs).
  • To assess how MEK inhibition affects anti-tumor immunity and immunotherapy response.

Main Methods:

  • In vitro and in vivo studies using MEK inhibitors.
  • Analysis of B regulatory cells (Bregs) in colorectal cancer models.
  • Evaluation of T cell infiltration and response to anti-PD1 immunotherapy.

Main Results:

  • MEK inhibition reduced B regulatory cells (Bregs) in vitro and in tumor-draining lymph nodes.
  • MEK inhibition did not impair anti-tumor humoral immunity.
  • B cells contributed to anti-tumor immunity during MEK inhibitor therapy.
  • MEK inhibition enhanced T cell infiltration and anti-PD1 immunotherapy response.

Conclusions:

  • MEK inhibition may decrease immunosuppressive B regulatory cells (Bregs).
  • MEK inhibition spares beneficial anti-tumor B cell functions.
  • Combined MEK inhibition and immunotherapy can enhance anti-tumor immunity.

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