Intratumoral immunotherapy relies on B and T cell collaboration

Antitumor T cell responses are the primary mediators of cancer immunotherapy. However, many other components of the immune system are needed for efficient T cell responses to be generated. Here, we developed a combinatorial approach where a Toll-like receptor 9 agonist (CpG) and Fc-fused IL-12 protein were injected together into just one of several tumor sites in a mouse. This combination led to body-wide (abscopal) therapeutic responses in multiple cancer models. These systemic responses were dependent not only on T cells but also on B cells. B cells were activated by the treatment and were required for optimal T cell activation. This cross-talk was dependent on MHC and was tumor antigen specific. The addition of an agonistic antibody against OX40 further enhanced T cell activation and therapeutic responses. Our data suggest that the combination of CpG, anti-OX40, and IL-12Fc may have success in patients with cancer and that B and T cell collaboration is crucial for the efficacy of this combination immunotherapy.

Automated summary

Antitumor T cell responses play a crucial role in cancer immunotherapy, but other immune system components are also necessary for effective T cell responses. This study demonstrates that combining Toll-like receptor 9 agonist CpG and Fc-fused IL-12 protein can induce body-wide therapeutic responses in multiple cancer models. These responses depend not only on T cells but also on B cells, which are activated by the treatment and required for optimal T cell activation. The addition of an agonistic antibody against OX40 further enhances T cell activation and therapeutic responses. These findings suggest the potential success of the combination of CpG, anti-OX40, and IL-12Fc in cancer patients and highlight the importance of B and T cell collaboration in this combination immunotherapy.