CTLA-4 blockade enhances germinal center reactions in lymph nodes that drive glioma-specific IgG production and glioma clearance

However, the involvement of B cell responses in anti-tumor and immunotherapy responses remains largely unexplored. Here, we show that activation of B cells in GCs of tumor-draining deep cervical LNs (dcLNs) is necessary for the efficacy of CTLA-4 immune checkpoint blockade in glioma in vivo.

We demonstrate that anti-CTLA-4 therapy enhances follicular helper T cell (Tfh) expansion in dcLNs, leading to GC B cell formation, class switching to IgG, and the generation of glioma-specific antibodies. Glioma-bearing mice lacking antibody-secreting cells did not benefit from CTLA-4 blockade. Furthermore, using our new in vivo reporter system, we show that distally-secreted glioma-specific IgG infiltrates the tumor microenvironment and triggers glioma cell phagocytosis.