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IL6 阳性癌相关成纤维细胞在梅克尔细胞癌发病机制中的作用:免疫微环境的可能调节因子

英文原题:Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment.

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Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment.

PubMed 2022/09/01(内容时间) Anticancer Res Q4 · IF 1.8(JCR 2025)

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研究概要

IL6 + CAFs 可能通过调节不同的 T 细胞亚群和功能,在很大程度上影响 MCC 的肿瘤免疫微环境。本研究为克服 MCC 免疫治疗耐药提供了一个可能的治疗靶点。

研究思路结论见上方概要

癌症相关成纤维细胞(CAFs)在 Merkel 细胞癌(MCC)发病机制中的作用仍不清楚。本研究旨在探讨 MCC 患者中 CAF 亚群的临床病理意义及其与TIL(肿瘤浸润淋巴细胞)(TILs)的关联。

对20例MCC患者及组织切片进行了临床病理特征及肿瘤团块周围微环境纤维化(MF)状态的评估。采用免疫组织化学方法检测MCC组织样本中的α-平滑肌肌动蛋白(α-SMA)阳性CAFs(α-SMA + CAFs)、白细胞介素-6阳性CAFs(IL6 + CAFs)、CD4阳性TILs(CD4 + TILs)和CD8阳性TILs(CD8 + TILs)。

在总共20例MCC患者中,12例(60%)检测到高MF,其与更差的无进展生存期显著相关(p=0.048),但与总生存期无关。CD4 + /CD8 + TIL在MCC组织中经常被检测到。在我们的队列中,高瘤内CD8 + TIL与更好的总生存期和无进展生存期显著相关(p=0.04和p=0.015)。11例(55.0%)患者检测到高SMA + CAF,10例(50.0%)患者检测到高IL6 + CAF。高IL6 + CAF与高瘤内CD8 + TIL之间发现负相关(p=0.005)。高IL6 + CAF患者比低IL6 + CAF患者表现出更差的总生存期/无进展生存期(p=0.022和p=0.035)。

展开英文摘要原文

Clinicopathological features and the status of microenvironment fibrosis (MF) around tumor masses were evaluated in 20 MCC patient and tissue sections. Alpha-smooth muscle actin ( -SMA)-positive CAFs ( -SMA + CAFs), interleukin-6-positive CAFs (IL6 + CAFs), CD4-positive TILs (CD4 + TILs), and CD8-positive TILs (CD8 + TILs) in MCC tissue samples were investigated using immunohistochemistry.

In a total of 20 MCC patients, high-MF was detected in 12 (60%) patients which was significantly associated with worse progression-free survival (p=0.048), but not with overall survival. CD4 + /CD8 + TILs were frequently detected in MCC tissues. High-intra-tumoral CD8 + TIL was significantly associated with better overall and progression-free survival (p=0.04 and p=0.015) in our cohort. High- SMA + CAFs were detected in 11 (55.0%) patients and high-IL6 + CAFs in 10 (50.0%) patients. A negative association was found between high-IL6 + CAF and high-intra-tumoral CD8 + TILs (p=0.005). Patients with high IL6 + CAFs showed worse overall/progression-free survival than patients with low-IL6 + CAFs (p=0.022 and p=0.035).

IL6 + CAFs may largely influence the tumor immune microenvironment of MCC by modulating distinct T-cell populations and functions. This study provides a possible therapeutic target to overcome resistance to immune therapies in MCC.

论文信息

作者
Zheng Z、Yoo DS、Li S、Pei M、Lee SG、Kim JY、Chung KY、Roh MR
第一作者单位
Department of Dermatology, Yanbian University Hospital, Yanji, P.R. China.China
通讯作者单位
Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; karenroh@yuhs.ac.South Korea
期刊
Anticancer research2022 Sep
原文标识
PubMed 36039447 · DOI 10.21873/anticanres.15936