Gut segmented filamentous Bacteria impedes growth of B16F10 subcutaneous tumors via modulating T cell function

Intestinal microbiota composition influences innate and adaptive immunity, both within and beyond the intestine. A prominent example of the latter is segmented filamentous bacteria (SFB), whose gut colonization reprograms alveolar macrophages (AM) and systemically shapes T cell polarity. We hypothesized that these impacts of SFB would influence anti-tumor immunity. We tested this hypothesis via intravenous and subcutaneous injection of B16F10 cells, which, respectively, models metastatic lung cancer and melanoma in mice. SFB colonization did not impact model lung cancer but suppressed melanoma growth and, concomitantly, prolonged survival. Such protection was completely lost in Rag1-deficient mice, indicating a requirement for adaptive immunity for the SFB-mediated tumor suppression. Concomitantly, SFB promoted infiltration of tumors by CD4⁺ and CD8⁺ T cells and, furthermore, enhanced their activation. The level of tumor suppression provided by SFB colonization was similar, but additive, to that conferred by immune checkpoint blockade. Thus, microbiota composition impacts T cell-mediated anti-tumor immunity in a site-specific manner. Mechanistic understanding of such interactions may inform cancer prevention and treatment.