美国匹兹堡大学Timothy W. Hand研究组发现微生物群特异性 T 滤泡辅助 (Tfh)细胞可驱动三级淋巴结构和针对结直肠癌 (CRC)的抗肿瘤免疫。这一研究成果发表在2021年12月2日出版的国际学术期刊《免疫学》上。

他们研究了微生物群特异性 T 细胞在抗CRC免疫中的作用。在结直肠癌小鼠模型中引入肝螺杆菌 (Hhep) 不会改变微生物景观，但会增加细胞毒性淋巴细胞的肿瘤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 Hhep 特异性 Tfh 细胞，增加结肠 Tfh 细胞的数量，并支持 Hhep+ 肿瘤相邻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 细胞过继转移到缺乏 Tfh 细胞 Bcl6fl/flCd4Cre 小鼠中可以恢复抗肿瘤免疫。因此，免疫原性肠道细菌的引入可以促进结肠中 Tfh 相关的抗肿瘤免疫，这表明了治疗 CRC 的方法。

据悉，肠道微生物群的组成与肿瘤进展和抗肿瘤免疫的功效有关。

附：英文原文

Title: Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

Author: Abigail E. Overacre-Delgoffe, Hannah J. Bumgarner, Anthony R. Cillo, Ansen H.P. Burr, Justin T. Tometich, Amrita Bhattacharjee, Tullia C. Bruno, Dario A.A. Vignali, Timothy W. Hand

Issue&Volume: 2021-12-02

Abstract: The composition of the intestinal microbiota is associated with both the developmentof tumors and the efficacy of anti-tumor immunity. Here, we examined the impact ofmicrobiota-specific T cells in anti-colorectal cancer (CRC) immunity. Introductionof Helicobacter hepaticus (Hhep) in a mouse model of CRC did not alter the microbial landscape but increased tumorinfiltration by cytotoxic lymphocytes and inhibited tumor growth. Anti-tumor immunitywas 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 Bcl6fl/flCd4Cre mice restored anti-tumor immunity. Thus, introduction of immunogenic intestinal bacteriacan promote Tfh-associated anti-tumor immunity in the colon, suggesting therapeuticapproaches for the treatment of CRC.

DOI: 10.1016/j.immuni.2021.11.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00494-5