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.

中文翻译：

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肿瘤内免疫治疗依赖于 B 细胞和 T 细胞协作

抗肿瘤 T 细胞反应是癌症免疫治疗的主要介质。然而，要产生有效的 T 细胞反应，还需要免疫系统的许多其他成分。在这里，我们开发了一种组合方法，将 Toll 样受体 9 激动剂 (CpG) 和融合 Fc 的 IL-12 蛋白一起注射到小鼠的几个肿瘤部位之一。这种组合导致了多种癌症模型中的全身（异位）治疗反应。这些全身反应不仅依赖于 T 细胞，还依赖于 B 细胞。B 细胞通过处理被激活并且是最佳 T 细胞激活所必需的。这种串扰依赖于 MHC 并且是肿瘤抗原特异性的。添加针对 OX40 的激动性抗体进一步增强了 T 细胞活化和治疗反应。