Department of Pathology, 539990AbderrahmanMami Hospital, Ariana, Tunisia.
Laboratory Research: LR18SP06, Public Minister, Tunisia.
Asian Cardiovasc Thorac Ann. 2022 Feb;30(2):177-184. doi: 10.1177/02184923211042129. Epub 2021 Sep 24.
Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas.
We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival.
Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( = 0.009), and a CD8/CD4 ratio ( = 0.008) were prognostic factors for overall survival. Complete surgical resection ( = 0.003), the forkhead box protein P3/CD8 ( = 0.005), and forkhead box protein P3/CD4 ( = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( = 0.004) and a CD8/CD4 ratio ( = 0.016) were independent predictors of overall survival.
Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.
肿瘤浸润淋巴细胞是宿主抗肿瘤反应的关键组成部分。因此，它们对包括非小细胞肺癌在内的癌症的演变有相当大的影响。尽管这一重要作用是共识，但文献中发表了许多关于肿瘤浸润淋巴细胞不同群体的预后作用的不一致结果。我们的工作旨在评估非小细胞肺癌肿瘤微环境中 CD8+、CD4+和叉头框蛋白 P3+淋巴细胞的预后影响。
我们进行了一项回顾性描述性研究，纳入了 2011 年至 2015 年期间在病理学系诊断并在同一家医院的肿瘤内科随访的非小细胞肺癌患者。通过免疫组织化学方法分析肿瘤浸润淋巴细胞的叉头框蛋白 P3、CD4 和 CD8。通过高倍镜（×400）手动计数对肿瘤内和基质标记的淋巴细胞进行定量。随后计算叉头框蛋白 P3+/CD8+、叉头框蛋白 P3+/CD4+和 CD8+/CD4+的比值。评估肿瘤浸润淋巴细胞的预后价值，包括总生存率、无复发生存率和无病生存率。
纳入 39 例患者。患者的平均年龄为 59.6 岁。完全手术切除（ = 0.009）和 CD8/CD4 比值（ = 0.008）是总生存率的预后因素。完全手术切除（ = 0.003）、叉头框蛋白 P3/CD8（ = 0.005）和叉头框蛋白 P3/CD4（ = 0.037）比值是无复发生存率的预后因素。CD8+肿瘤浸润淋巴细胞率（ = 0.037）是无病生存率的预后因素，阈值为 67.8/高倍视野。当仅考虑腺癌和鳞状细胞癌时，微观亚型（ = 0.037）是无复发生存率的预后因素。多变量分析显示，年龄（ = 0.004）和 CD8/CD4 比值（ = 0.016）是总生存率的独立预测因素。
尽管我们的研究存在局限性，但我们的结果证实了肿瘤浸润淋巴细胞在非小细胞肺癌中的预后价值，以及联合量化其不同亚群的重要性。
