肿瘤浸润淋巴细胞亚群及其在口腔鳞状细胞癌中的个体预后影响。
Tumour-infiltrating lymphocyte subsets and their individual prognostic impact in oral squamous cell carcinoma.
发表日期:2023 Sep 12
作者:
Aanchal Kakkar, Rishikesh Thakur, Diya Roy, Ridhi Sood, Atul Sharma, Rajeev Kumar Malhotra, Alok Thakar
来源:
Cellular & Molecular Immunology
摘要:
目前对于口腔鳞状细胞癌(OSCC)的认识尚不完整,特别是与预后因素相关的,这可能导致治疗反应和患者预后存在显著异质性。本研究旨在通过一项回顾性观察性研究,评估个体肿瘤浸润淋巴细胞(TIL)亚群在预后中的影响,作为其潜在解释。使用免疫组化技术定量评估了50例行手术治疗的OSCC病例中CD3+、CD20+、CD4+、CD8+和FOXP3+ TIL亚群的细胞密度。将结果与无病生存期(DFS)和总生存期(OS)进行相关分析。使用接受者操作特征曲线分析和优德指数确定了具有预后意义的临界值。CD3+、CD4+、CD8+、CD20+和FOXP3+ TIL的平均计数分别为243、52、132、53和116个细胞/高倍视野。高CD8+和低FOXP3+ TIL计数,以及高CD8∶FOXP3比率与较长的DFS和OS相关,同时与改善肿瘤-宿主界面参数相关。宿主免疫反应及其与癌细胞的相互作用对OSCC的预后有重要影响,其中某些TIL亚群比其他亚群更具临床相关性。高细胞毒性T细胞(CD8)和低调节性T细胞(Treg)(FOXP3)计数,以及高细胞毒性T细胞与调节性T细胞的比值(CD8∶FOXP3)与有利的预后显著相关。这些结果可能为寻找能够通过减少浸润的FOXP3阳性淋巴细胞,并改变它们的信号通路来重构肿瘤免疫微环境的新型治疗药物提供有价值的线索。© 作者(或其雇主)2023。不可进行商业再利用。详见权利和许可。由BMJ发布。
Current understanding of oral squamous cell carcinoma (OSCC) is incomplete with regard to prognostic factors that lead to the considerable heterogeneity in treatment response and patient outcomes. We aimed to evaluate the impact of individual tumour-infiltrating lymphocyte (TIL) subsets on prognosis as a possible rationale for this, in a retrospective observational study.Immunohistochemistry was performed to quantitatively assess cell densities of CD3+, CD20+, CD4+, CD8+ and FOXP3+TIL subsets in 50 surgically treated OSCC cases. Results were correlated with disease-free survival (DFS) and overall survival (OS). Receiver operating characteristic curve analysis and Youden index were applied to determine prognostically significant cut-off values.Mean counts for CD3+, CD4+, CD8+, CD20+ and FOXP3+TILs were 243, 52, 132, 53 and 116 cells per high power field, respectively. High CD8+ and low FOXP3+TIL counts, and high ratio of CD8:FOXP3 were significantly associated with longer DFS and OS, as well as with improved tumour-host interface parameters.Host immune response and its interaction with cancer cells have a significant impact on OSCC outcomes, with some TIL subsets being more clinically relevant than others. High cytotoxic T-cell (CD8) and low Treg (FOXP3) counts, and high cytotoxic T-cell to Treg (CD8:FOXP3) ratio are significantly associated with favourable prognosis. These results may serve as a leading point in identifying novel therapeutic agents that can redesign the tumour immune microenvironment by reducing infiltrating FOXP3-lymphocytes, and modifying their signalling pathways.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.