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Significance Bacillus Calmette–Guérin (BCG) therapy is one of the oldest tumor immunotherapies, but its mechanism remains unknown. Herein we show that BCG therapy induces tumor-specific T cell-dependent immunity that is predominantly mediated by CD4 T cells in a manner distinct from other tumor immunotherapies. These immunologic insights may allow investigation into biomarkers that could predict the efficacy of BCG in human cancer patients.

Bacterial immunotherapy for cancer induces CD4-dependent tumor-specific immunity through tumor-intrinsic interferon-γ signaling