Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells

IF 4.8 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Neoplasia Pub Date : 2024-10-24 DOI:10.1016/j.neo.2024.101072
Ran Ran , Martin Trapecar , Douglas K. Brubaker
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Abstract

Gamma delta T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including poised effector-like T cells, tissue-resident memory T cells, progenitor exhausted-like T cells, and exhausted T cells, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. We proposed anti-tumor γδ T effector cells may arise from tissue-resident progenitor cells based on the trajectory analysis. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology.
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对人类结直肠癌 scRNA-seq 的系统分析显示,γ δ T 细胞产生促肿瘤 IL-17 的潜力有限。
γδT细胞具有细胞毒性,在抗肿瘤免疫中发挥着重要作用。然而,γδT 细胞在结直肠癌(CRC)肿瘤微环境中产生促致癌白细胞介素-17(IL-17)的作用和程度仍存在争议。在这项研究中,我们重新分析了已发表的 9 个人类 CRC 全组织单细胞 RNA 测序数据集,在 165 名人类 CRC 患者的肿瘤组织或邻近正常组织的 951 785 个细胞总数中鉴定出了 18 483 个 γδ T 细胞。我们的研究结果证实,肿瘤浸润的 γδ T 细胞在肿瘤和邻近正常组织中都表现出高度的细胞毒性相关转录,但关键的是,没有一个 γδ T 细胞集群显示出产生 IL-17 的潜能。我们还发现了各种γδT细胞亚群,包括蓄势待发的效应样T细胞、组织驻留记忆T细胞、衰竭样T细胞祖细胞和衰竭T细胞,并注意到与正常区域的T细胞相比,肿瘤浸润的γδT细胞中细胞毒性分子的表达增加。根据轨迹分析,我们提出抗肿瘤γδT效应细胞可能来自组织驻留的祖细胞。我们的研究表明,CRC 中的γδ T 细胞主要作为细胞毒性效应细胞而非 IL-17 生成细胞发挥作用,这减轻了人们对其在 CRC 中潜在促肿瘤作用的担忧,凸显了准确描述这些细胞对癌症免疫疗法研究的重要性,以及在癌症免疫学研究中小鼠和人类免疫系统之间不可忽视的跨物种差异。
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来源期刊
Neoplasia
Neoplasia 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
82
审稿时长
26 days
期刊介绍: Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.
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