The transcription factor c-Myb is overexpressed in many different types of solid tumors, including colorectal cancer. However, its exact role in tumorigenesis is unclear. In this study, we show that tumor-intrinsic c-Myb expression in mouse models of colon cancer and melanoma suppresses tumor growth. Although no differences in proliferation, apoptosis, and angiogenesis of tumors were evident in tumors with distinct levels of c-Myb expression, we observed changes in intratumoral immune cell infiltrates. MC38 tumors with upregulated c-Myb expression showed increased numbers of CD103+ dendritic cells and eosinophils, but decreased tumor-associated macrophages (TAM). Concomitantly, an increase in the number of activated cytotoxic CD8+ T cells upon c-Myb upregulation was observed, which correlated with a pro-inflammatory tumor microenvironment and increased numbers of M1 polarized TAMs. Mechanistically, c-Myb upregulation in immunogenic MC38 colon cancer cells resulted in enhanced expression of immunomodulatory genes, including those encoding β2-microglobulin and IFNβ, and decreased expression of the gene encoding the chemokine receptor CCR2. The increased numbers of activated cytotoxic CD8+ T cells contributed to tumor growth attenuation. In poorly immunogenic CT26, LLC, and B16-BL6 tumor cells, c-Myb upregulation did not affect the immunomodulatory gene expression. Despite this, c-Myb upregulation led to reduced B16-BL6 tumor growth but it did not affect tumor growth of CT26 and LLC tumors. Altogether, we postulate that c-Myb functions as a tumor suppressor in a tumor cell-type specific manner and modulates antitumor immunity.

Comprehensive Cancer Center Zurich University Hospital of Zurich Zurich Switzerland

Department of Computer Science University of Toronto Toronto Canada

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Immunology University Hospital Zurich Zurich Switzerland

Department of Medical Biophysics University of Toronto Toronto Canada

Faculty of Dentistry University of Toronto Toronto Canada

Faculty of Medicine University of Zurich Zurich Switzerland

Institute of Neuroimmunology Slovak Academy of Sciences Bratislava Slovakia

Institute of Physiology University of Zurich Zurich Switzerland

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Osteoarthritis Research Program Division of Orthopedic Surgery Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases Krembil Research Institute Toronto Western Hospital Toronto Canada

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