PD-L1+ Lymphocytes Are Associated with CD4+, Foxp3+CD4+, IL17+CD4+ T Cells and Subtypes of Macrophages in Resected Early-Stage Non-Small Cell Lung Cancer

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10827
• Main Authors: Gurevičienė, Giedrė, Matulionė, Jurgita, Poškienė, Lina, Miliauskas, Skaidrius, Žemaitis, Marius
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.10.2024; MDPI
• Subjects: Aged; B7-H1 Antigen - metabolism; Biomarkers; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Care and treatment; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Chronic obstructive pulmonary disease; Female; Forkhead Transcription Factors - metabolism; Genotype & phenotype; Health aspects; Humans; Interleukin-17 - metabolism; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Middle Aged; Neoplasm Staging; Physiological aspects; Prognosis; Tumor Microenvironment - immunology; Tumors; Lithuania; non-small cell lung cancer; macrophages; programmed death-ligand 1; tumour microenvironment; lymphocytes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910827

The non-canonical PD-L1 pathway revealed that programmed-death ligand 1 (PD-L1) expression in immune cells also plays a crucial role in immune response. Moreover, immune cell distribution in a tumour microenvironment (TME) is pivotal for tumour genesis. However, the results remain controversial and further research is needed. Distribution of PD-L1-positive (PD-L1+) tumour-infiltrating lymphocytes in the context of TME was assessed in 72 archival I–III stage surgically resected NSCLC tumour specimens. Predominant PD-L1+ lymphocyte distribution in the tumour stroma, compared to islets, was found (p = 0.01). Higher PD-L1+ lymphocyte infiltration was detected in smokers due to their predominance in the stroma. High PD-L1+ lymphocyte infiltration in tumour stroma was more common in tumours with higher CD4+ T cell infiltration in islets and stroma, Foxp3+CD4+ T cell infiltration in islets and lover M1 macrophage infiltration in the stroma (p = 0.034, p = 0.034, p = 0.005 and p = 0.034 respectively). Meanwhile, high PD-L1+ lymphocyte infiltration in islets was predominantly found in tumours with high levels of IL-17A+CD4+ T cells in islets and Foxp3+CD4+ T cells in islets and stroma (p = 0.032, p = 0.009 and p = 0.034, respectively). Significant correlations between PD-L1+ lymphocytes and tumour-infiltrating CD4+, Foxp3+CD4+, IL-17A+CD4+ T cells and M2 macrophages were found. An analysis of the tumour-immune phenotype revealed a significant association between PD-L1 expression and IL17+CD4+ and Foxp3+CD4+ immune phenotypes. PD-L1+ lymphocytes are associated with the distribution of CD4+, Foxp3+CD4+, IL17A+CD4+ T cells, M1 and M2 macrophages in TME of resected NSCLC.