Intratumoral immunotherapy relies on B and T cell collaboration

Sci Immunol. 2022 May 27;7(71):eabn5859. doi: 10.1126/sciimmunol.abn5859. Epub 2022 May 27.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies
  • Humans
  • Immunotherapy
  • Mice
  • Neoplasms* / therapy
  • T-Lymphocytes*

Substances

  • Adjuvants, Immunologic
  • Antibodies