The transcription factor BACH2 promotes tumor immunosuppression

Rahul Roychoudhuri, Robert L. Eil, David Clever, Christopher A. Klebanoff, Madhusudhanan Sukumar, Francis M. Grant, Zhiya Yu, Gautam Mehta, Hui Liu, Ping Jin, Yun Ji, Douglas C. Palmer, Jenny H. Pan, Anna Chichura, Joseph G. Crompton, Shashank J. Patel, David Stroncek, Ena Wang, Francesco M. Marincola, Klaus OkkenhaugLuca Gattinoni, Nicholas P. Restifo

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

The immune system has a powerful ability to recognize and kill cancer cells, but its function is often suppressed within tumors, preventing clearance of disease. Functionally diverse innate and adaptive cellular lineages either drive or constrain immune reactions within tumors. The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its role in controlling tumor immunity has not been elucidated. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. However, augmented tumor clearance in the absence of Bach2 was dependent upon the adaptive immune system. Analysis of tumor-infiltrating lymphocytes from Bach2-deficient mice revealed high frequencies of rapidly proliferating effector CD4+ and CD8+ T cells that expressed the inflammatory cytokine IFN-γ. Effector T cell activation coincided with a reduction in the frequency of intratumoral Foxp3+ Tregs. Mechanistically, BACH2 promoted tumor immunosuppression through Treg-mediated inhibition of intratumoral CD8+ T cells and IFN-γ. These findings demonstrate that BACH2 is a key component of the molecular program of tumor immunosuppression and identify therapeutic targets for the reversal of immunosuppression in cancer.

Original languageEnglish (US)
Pages (from-to)599-604
Number of pages6
JournalJournal of Clinical Investigation
Volume126
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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