应用多重免疫组化技术研究头颈部鳞状细胞癌新辅助免疫治疗后肿瘤免疫微环境的变化。

IF 4 2区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral oncology Pub Date : 2025-02-01 DOI:10.1016/j.oraloncology.2024.107151

Zhaohong An , Xiwei Zhang , Zhaoyang Wang , Dilinaer Wusiman , Xiaohui Zhao , Lin Li , Lei Guo , Minghui Wei , Wenbin Li , Changming An

{"title":"应用多重免疫组化技术研究头颈部鳞状细胞癌新辅助免疫治疗后肿瘤免疫微环境的变化。","authors":"Zhaohong An , Xiwei Zhang , Zhaoyang Wang , Dilinaer Wusiman , Xiaohui Zhao , Lin Li , Lei Guo , Minghui Wei , Wenbin Li , Changming An","doi":"10.1016/j.oraloncology.2024.107151","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).</div></div><div><h3>Methods</h3><div>HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).</div></div><div><h3>Results</h3><div>The populations of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3<sup>+</sup> T cells and LAG3<sup>+</sup> T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8<sup>+</sup> T cells infiltrating in the tumor marginal zone.</div></div><div><h3>Conclusion</h3><div>The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3<sup>+</sup> T cells and LAG3<sup>+</sup> T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"161 ","pages":"Article 107151"},"PeriodicalIF":4.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry\",\"authors\":\"Zhaohong An , Xiwei Zhang , Zhaoyang Wang , Dilinaer Wusiman , Xiaohui Zhao , Lin Li , Lei Guo , Minghui Wei , Wenbin Li , Changming An\",\"doi\":\"10.1016/j.oraloncology.2024.107151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).</div></div><div><h3>Methods</h3><div>HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).</div></div><div><h3>Results</h3><div>The populations of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3<sup>+</sup> T cells and LAG3<sup>+</sup> T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8<sup>+</sup> T cells infiltrating in the tumor marginal zone.</div></div><div><h3>Conclusion</h3><div>The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3<sup>+</sup> T cells and LAG3<sup>+</sup> T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses.</div></div>\",\"PeriodicalId\":19716,\"journal\":{\"name\":\"Oral oncology\",\"volume\":\"161 \",\"pages\":\"Article 107151\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S136883752400469X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S136883752400469X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

摘要

目的：优化头颈部鳞状细胞癌（HNSCC）的临床决策具有挑战性，因为对新辅助免疫治疗（NIT）后疾病的免疫细胞动力学和免疫检查点调节的理解不明确。方法：将新辅助治疗前后采集的HNSCC活检标本根据治疗反应分为病理反应组（PR）和非病理反应组（NPR），采用多重免疫组织化学（m-IHC）标记免疫细胞和检查点的表达。结果：PR组治疗前组织中CD4+ T细胞、CD8+ T细胞、调节性T细胞（Treg）、PD-1、PD-L1的数量明显高于NPR组，PR组log-转化阳性细胞密度+ T细胞、LAG3+ T细胞的P值较NPR组明显降低，且P + T细胞浸润于肿瘤边缘区，治疗后与治疗前表达比差异有统计学意义。结论：T细胞的存在对HNSCC患者对新辅助免疫治疗的反应具有重要的预测能力。此外，治疗后部分缓解（PR）组的TIM3+ T细胞和LAG3+ T细胞显著低于非部分缓解（NPR）组。这项研究有助于理解免疫细胞反应中发生的生理变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry

查看原文本刊更多论文

The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry

Objective

Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).

Methods

HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).

Results

The populations of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3⁺ T cells and LAG3⁺ T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8⁺ T cells infiltrating in the tumor marginal zone.

Conclusion

The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3⁺ T cells and LAG3⁺ T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Oral oncology 医学-牙科与口腔外科

CiteScore

8.70

自引率

10.40%

发文量

505

审稿时长

20 days

期刊介绍： Oral Oncology is an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, editorials, and commentaries relating to the etiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment and management of patients with neoplasms in the head and neck. Oral Oncology is of interest to head and neck surgeons, radiation and medical oncologists, maxillo-facial surgeons, oto-rhino-laryngologists, plastic surgeons, pathologists, scientists, oral medical specialists, special care dentists, dental care professionals, general dental practitioners, public health physicians, palliative care physicians, nurses, radiologists, radiographers, dieticians, occupational therapists, speech and language therapists, nutritionists, clinical and health psychologists and counselors, professionals in end of life care, as well as others interested in these fields.