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美国弗雷德·哈钦森癌症研究中心Martin Prlic课题组在研究中取得进展。他们的研究揭示与组织炎症相关人类肿瘤免疫改变。相关论文发表在2022年5月11日出版的《自然》杂志上。

为了揭示肿瘤微环境中的免疫改变，研究人员使用互补的单细胞分析方法探究了人头颈部鳞状细胞癌和与病灶匹相关非恶性炎症组织中的免疫浸润。研究发现肿瘤和发炎组织中免疫细胞的组成和表型有很大的重叠。计算分析确定了肿瘤富集组织与免疫细胞间的相互作用，其中一个特征是产生大量的调节性T(Treg)细胞群，这些细胞在肿瘤中高度富集，并通过ICOS和IL-1Ⅰ型受体(IL1R1)共表达在血液和组织的所有造血衍生细胞中特异性存在。

该研究提供的证据表明这些肿瘤内IL1R1⁺ Treg细胞对抗原有反应，并且与IL1R1^- Treg细胞相比发挥具有更强的抑制功能并进行克隆扩增。除了确定炎性组织和肿瘤之间广泛的免疫一致性以及与疾病直接相关肿瘤特异性变化外，该工作还为从一般炎症相关模式中解析疾病特异性变化提供了思路。

据了解，免疫疗法在癌症治疗方面取得了显著的成功，但仍存在许多挑战。当前治疗方法的一个固有缺陷是治疗靶向途径不仅限于肿瘤，还存在于其他组织微环境中，这使治疗复杂化。尽管已有许多与肿瘤微环境炎症有关的研究，但对肿瘤独特免疫改变的理解受到发炎人体组织中免疫细胞群研究缺乏的限制。

附：英文原文

Title: Extricating human tumour immune alterations from tissue inflammation

Author: Mair, Florian, Erickson, Jami R., Frutoso, Marie, Konecny, Andrew J., Greene, Evan, Voillet, Valentin, Maurice, Nicholas J., Rongvaux, Anthony, Dixon, Douglas, Barber, Brittany, Gottardo, Raphael, Prlic, Martin

Issue&Volume: 2022-05-11

Abstract: Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1 Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.

DOI: 10.1038/s41586-022-04718-w

Source: https://www.nature.com/articles/s41586-022-04718-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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