Is It Unnecessary to Assess Tumor Stroma-Infiltrating Lymphocytes in Localized Lung Adenocarcinomas?

Background: During the last decade, more attention was paid to the tumor cell microenvironment, especially to tumor stroma-infiltrating lymphocytes (TILs). This study aimed to assess the prognostic impact of different TILs subpopulations and PD-L1 positive tumor cells in localized lung adenocarcinomas.

Materials and methods: We conducted a retrospective descriptive study, which included localized adenocarcinomas diagnosed in the department of pathology and resected in the Thoracic Surgery Department of the same hospital between 2015 and 2020. TILs were analyzed using the immunohistochemical method for Fox-P3, CD4, CD8, CD20, and CD3. Besides, the PD-L1 antibody was used to assess tumor cell expression. Intra-tumoral and stromal labeled lymphocytes were quantified by manual counting at high magnification (X400). Fox-P3+/CD8+, Fox-P3+/CD4+, FoxP3+/PD-L1+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of TILs was assessed with respect to overall survival (OS) and recurrence free survival (ReFS).

Results: A total of 44 localized adenocarcinomas were included. In the univariate analysis, the prognostic factors influencing OS included gender, adenocarcinoma subtype, Tumor-Infiltrating Lymphocyte (TIL) score, TIL grade, PD-L1 expression, PD-L1 grade, tumor immunity in the microenvironment, and the expressions of various immune markers: CD3, CD4, CD8, CD20, and FoxP3. The analysis also considered the FoxP3 ratio, FIL score, and different ratios involving immune markers, such as CD8/CD4 ratio, FoxP3/CD8 ratio, FoxP3/CD4 ratio, and FoxP3/PD-L1 ratio. The prognostic factors influencing the ReFS consisted of gender, the adenocarcinoma subtype, TIL score, TIL grade, PD-L1, PD-L1 grade, TIM, CD8 expression, CD20 expression, FIL score, Fox-P3/CD8 ratio, Fox-P3/CD4 ratio, and Fox-P3/PD-L1 ratio. Multivariate analysis revealed no independent predictive factors of OS or ReFS.

Conclusion: Despite the limitations of this study, the results highlighted that TILs may not represent an independent prognostic factor in localized adenocarcinomas and don't play a major role in comparison to the tumor stage.