Transcriptomics

Dataset Information

8

The transcription factor BACH2 is required to establish immunosuppression within tumors


ABSTRACT: Through a diversity of functional lineages, cells of the innate and adaptive immune system either drive or constrain immune reactions within tumors. Thus, while the immune system has a powerful ability to recognize and kill cancer cells, this function is often suppressed preventing clearance of disease. The transcription factor (TF) BACH2 controls the differentiation and function of multiple innate and adaptive immune lineages, but its role in regulating tumor immunity is not known. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. We found that growth of subcutaneously implanted tumors was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity but was dependent upon adaptive immunity. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression. These findings demonstrate that BACH2 is a key component of the molecular programme of tumor immunosuppression and identify a new target for development of therapies aimed at reversing immunosuppression in cancer. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression.

ORGANISM(S): Mus musculus  

SUBMITTER: Gautam Mehta   Douglas C Palmer  David Clever  Robert L Eil  PING JIN  Rahul Roychoudhuri  Hui Liu  Ping Jin  Zhiya Yu  Christopher A Klebanoff  Yun Ji  Madhusudhanan Sukumar 

PROVIDER: E-GEOD-74653 | ArrayExpress | 2016-06-01

SECONDARY ACCESSION(S): GSE74653PRJNA301072

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2013-06-27 | E-GEOD-45975 | ArrayExpress
| GSE97939 | GEO
2013-11-14 | E-GEOD-52337 | ArrayExpress
| GSE74957 | GEO
2013-11-01 | E-GEOD-42598 | ArrayExpress
| GSE77857 | GEO
2016-03-10 | E-GEOD-67918 | ArrayExpress
| phs001824 | dbGaP
| GSE87335 | GEO
2012-01-18 | E-GEOD-28130 | ArrayExpress