BCG-Induced Tumor Immunity Requires Tumor-Intrinsic CIITA Independent of MHC-II

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Bacillus Calmette-Guérin (BCG) is a standard treatment for non-muscle-invasive bladder cancer.
• The precise mechanisms underlying BCG's anti-tumor immunity are not fully understood.
• Predicting patient response to BCG remains a challenge.

Purpose of the Study:

• To elucidate the downstream signaling components of the interferon-gamma receptor (IFNGR) critical for BCG immunotherapy response.
• To identify molecular factors within tumor cells that mediate BCG-induced immunity.
• To explore potential biomarkers for predicting BCG efficacy.

Main Methods:

• Investigated the role of the class II transactivator CIITA in BCG immunotherapy.
• Utilized tumor cell models to assess the requirement of CIITA for T-cell activation and anti-tumor immunity.
• Examined the relationship between CIITA, MHC-II presentation, and broader transcriptional programs.

Main Results:

• Tumor cell-intrinsic expression of CIITA is essential for BCG-induced CD4 T-cell responses and anti-tumor immunity.
• CIITA's role in BCG responsiveness is independent of its canonical function in MHC-II antigen presentation.
• CIITA regulates a wider tumor-intrinsic transcriptional program linked to immune pathways.

Conclusions:

• CIITA is a critical mediator of BCG immunotherapy efficacy in bladder cancer.
• The function of CIITA in BCG response is distinct from its role in antigen presentation.
• Tumor cell CIITA status may inform the selection of immunotherapy, potentially differentiating BCG from PD-1 inhibitors.