R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224, USA; Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224, USA; Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
Immunity. 2021 Dec 14;54(12):2812-2824.e4. doi: 10.1016/j.immuni.2021.11.003. Epub 2021 Dec 2.
The composition of the intestinal microbiota is associated with both the development of tumors and the efficacy of anti-tumor immunity. Here, we examined the impact of microbiota-specific T cells in anti-colorectal cancer (CRC) immunity. Introduction of Helicobacter hepaticus (Hhep) in a mouse model of CRC did not alter the microbial landscape but increased tumor infiltration by cytotoxic lymphocytes and inhibited tumor growth. Anti-tumor immunity was independent of CD8 T cells but dependent upon CD4 T cells, B cells, and natural killer (NK) cells. Hhep colonization induced Hhep-specific T follicular helper (Tfh) cells, increased the number of colon Tfh cells, and supported the maturation of Hhep+ tumor-adjacent tertiary lymphoid structures. Tfh cells were necessary for Hhep-mediated tumor control and immune infiltration, and adoptive transfer of Hhep-specific CD4 T cells to Tfh cell-deficient Bcl6Cd4 mice restored anti-tumor immunity. Thus, introduction of immunogenic intestinal bacteria can promote Tfh-associated anti-tumor immunity in the colon, suggesting therapeutic approaches for the treatment of CRC.
肠道微生物组的组成与肿瘤的发生和抗肿瘤免疫的疗效有关。在这里，我们研究了肠道微生物特异性 T 细胞在抗结直肠癌 (CRC) 免疫中的作用。在 CRC 的小鼠模型中引入幽门螺杆菌 (Hhep) 不会改变微生物景观，但会增加细胞毒性淋巴细胞对肿瘤的浸润，并抑制肿瘤生长。抗肿瘤免疫不依赖于 CD8 T 细胞，但依赖于 CD4 T 细胞、B 细胞和自然杀伤 (NK) 细胞。Hhep 定植诱导了 Hhep 特异性滤泡辅助 T (Tfh) 细胞，增加了结肠 Tfh 细胞的数量，并支持了 Hhep+肿瘤相关三级淋巴结构的成熟。Tfh 细胞是 Hhep 介导的肿瘤控制和免疫浸润所必需的，将 Hhep 特异性 CD4 T 细胞过继转移到 Tfh 细胞缺陷的 Bcl6Cd4 小鼠中，恢复了抗肿瘤免疫。因此，引入免疫原性肠道细菌可以促进结肠中与 Tfh 相关的抗肿瘤免疫，为 CRC 的治疗提供了新的治疗方法。
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