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E-GEOD-74653 - The transcription factor BACH2 is required to establish immunosuppression within tumors

Status
Released on 1 June 2016, last updated on 4 June 2016
Organism
Mus musculus
Samples (10)
Array (1)
Protocols (6)
Description
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.
Experiment type
transcription profiling by array 
Contacts
PING JIN <PJIN@CC.NIH.GOV>, Christopher A Klebanoff, David Clever, Douglas C Palmer, Gautam Mehta, Hui Liu, Madhusudhanan Sukumar, Ping Jin, Rahul Roychoudhuri, Robert L Eil, Yun Ji, Zhiya Yu
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-74653.idf.txt
Sample and data relationshipE-GEOD-74653.sdrf.txt
Raw data (1)E-GEOD-74653.raw.1.zip
Processed data (1)E-GEOD-74653.processed.1.zip
Array designA-AFFY-45.adf.txt
Links