Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma.

IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Gastroenterology Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI:10.1007/s00535-024-02120-z
Takumi Habu, Shogo Kumagai, Hideaki Bando, Takeshi Fujisawa, Saori Mishima, Daisuke Kotani, Masaki Nakamura, Hidehiro Hojo, Shingo Sakashita, Takahiro Kinoshita, Tomonori Yano, Shuichi Mitsunaga, Hiroyoshi Nishikawa, Shohei Koyama, Takashi Kojima
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Abstract

Background: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment.

Methods: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC.

Results: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8+ T cells and conventional CD4+ T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1+CD8+ T cells in the tumor after CRT could predict a confirmed complete response and favorable survival.

Conclusions: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1+CD8+ T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment.

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对无法切除的局部晚期食管鳞状细胞癌,确定性化放疗可诱导T细胞炎症肿瘤微环境。
背景:化放疗(CRT)可调节包括食管癌在内的多种癌症类型的肿瘤免疫微环境,通过上调肿瘤特异性抗原和免疫检查点分子在肿瘤中的表达,可能诱导免疫原性和免疫抑制。CRT对食管鳞状细胞癌(ESCC)免疫改变的预后影响仍存在争议,因为缺乏使用CRT前后配对临床标本进行的详细免疫学分析。我们的目的是阐明 CRT 引起的肿瘤微环境免疫学变化,并阐明其对临床反应和预后的重要预测作用以及后续程序性细胞死亡蛋白 1(PD-1)抑制剂治疗的必要性:在这项研究中,我们使用多重免疫组化技术对CRT前后不可切除的局部晚期ESCC患者的配对活检标本进行了全面的免疫学分析:结果:CRT明显增加了CD8+ T细胞和常规CD4+ T细胞的瘤内浸润和PD-1表达,但减少了调节性T细胞的浸润和肿瘤相关巨噬细胞的聚集。对肿瘤浸润T细胞表型的多变量分析表明,CRT后肿瘤内PD-1+CD8+ T细胞的密度可预测确诊的完全反应和良好的生存期:本研究表明,CRT改善了不可切除的局部晚期ESCC的免疫学特征,并发现PD-1+CD8+ T细胞的密度是预后的预测因素。这一发现支持了后续PD-1抑制剂治疗的必要性。
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来源期刊
Journal of Gastroenterology
Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
12.20
自引率
1.60%
发文量
99
审稿时长
4-8 weeks
期刊介绍: The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.
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