Department of Pulmonology, Medical Academy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Department of Pathology, Medical Academy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Int J Mol Sci. 2024 Oct 9;25(19):10827. 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 ( = 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, Foxp3CD4 T cell infiltration in islets and lover M1 macrophage infiltration in the stroma ( = 0.034, = 0.034, = 0.005 and = 0.034 respectively). Meanwhile, high PD-L1 lymphocyte infiltration in islets was predominantly found in tumours with high levels of IL-17ACD4 T cells in islets and Foxp3CD4 T cells in islets and stroma ( = 0.032, = 0.009 and = 0.034, respectively). Significant correlations between PD-L1 lymphocytes and tumour-infiltrating CD4, Foxp3CD4, IL-17ACD4 T cells and M2 macrophages were found. An analysis of the tumour-immune phenotype revealed a significant association between PD-L1 expression and IL17CD4 and Foxp3CD4 immune phenotypes. PD-L1 lymphocytes are associated with the distribution of CD4, Foxp3CD4, IL17ACD4 T cells, M1 and M2 macrophages in TME of resected NSCLC.
非典型 PD-L1 通路表明，免疫细胞中程序性死亡配体 1（PD-L1）的表达也在免疫反应中发挥关键作用。此外，肿瘤微环境（TME）中免疫细胞的分布对于肿瘤发生至关重要。然而，结果仍存在争议，需要进一步研究。在 72 例手术切除的 I-III 期 NSCLC 肿瘤标本的 TME 中评估了 PD-L1 阳性（PD-L1）肿瘤浸润淋巴细胞的分布。与胰岛相比，发现肿瘤基质中 PD-L1 阳性淋巴细胞的分布为主（=0.01）。由于其在基质中的优势，吸烟者中检测到更高的 PD-L1 淋巴细胞浸润。在胰岛和基质中具有较高 CD4 T 细胞浸润、胰岛中 Foxp3CD4 T 细胞浸润和基质中较低 M1 巨噬细胞浸润的肿瘤中，肿瘤基质中 PD-L1 淋巴细胞浸润较高（=0.034，=0.034，=0.005 和=0.034 分别）。同时，在胰岛中具有高水平的 IL-17ACD4 T 细胞和胰岛及基质中 Foxp3CD4 T 细胞的肿瘤中，主要发现胰岛中 PD-L1 淋巴细胞浸润较高（=0.032，=0.009 和=0.034，分别）。PD-L1 淋巴细胞与肿瘤浸润 CD4、Foxp3CD4、IL-17ACD4 T 细胞和 M2 巨噬细胞之间存在显著相关性。肿瘤免疫表型分析显示 PD-L1 表达与 IL17CD4 和 Foxp3CD4 免疫表型之间存在显著相关性。PD-L1 淋巴细胞与 CD4、Foxp3CD4、IL17ACD4 T 细胞、M1 和 M2 巨噬细胞在切除的 NSCLC 的 TME 中的分布相关。
