Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas

Author:

Mlika Mona123ORCID,Saidi Ayoub123,Mejri Nesrine234,Abdennadher Mehdi235,Haddouchi Chokri12,Labidi Soumeya4,Khiari Hyem6,Boussen Hamouda34,Hsairi Mohamed36,Mezni Faouzi123

Affiliation:

1. Department of Pathology, AbderrahmanMami Hospital, Ariana, Tunisia

2. Laboratory Research: LR18SP06, Public Minister, Tunisia

3. Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia

4. Department of Medical Oncology, Abderrahman Mami Hospital, Ariana, Tunisia

5. Department of Thoracic Surgery, Abderrahman Mami Hospital, Ariana, Tunisia

6. Department of Epidemiology, Salah Azaiz Institute, Tunis, Tunisia

Abstract

Introduction 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. Methods 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. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion 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.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Pulmonary and Respiratory Medicine,General Medicine,Surgery

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