ABSTRACT
BACKGROUND/AIM: We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. MATERIALS AND METHODS: Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. RESULTS: Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. CONCLUSION: The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.
Subject(s)
B7-H1 Antigen/antagonists & inhibitors , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lymphocytes, Tumor-Infiltrating/immunology , Vascular Endothelial Growth Factor A/metabolism , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Female , Humans , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Progression-Free Survival , Tumor MicroenvironmentABSTRACT
BACKGROUND/AIM: There is no clear evidence in the literature regarding the regulation of programmed cell death-ligand 1 (PD-L1) expression by cyclo-oxygenase-2 (COX2). In this study, whether PD-L1 expression was regulated by COX2 activity was examined in vitro. MATERIALS AND METHODS: Resected lung cancer specimens were analyzed for PD-L1 and COX2 expression by immunohistochemical analysis. Next, co-localization of PD-L1 and COX2 expression was analyzed by double-fluorescence staining. Lastly, the effect of COX2 inhibition on the expression of PD-L1 was examined using lung cancer cell lines. RESULTS: PD-L1 expression was significantly correlated with COX2 expression in the resected specimens. The majority of cancer cells that expressed PD-L1 also co-expressed COX2. However, treatment of lung cancer cell lines with a COX2 inhibitor had no impact on PD-L1 expression. CONCLUSION: Our results suggest that COX2 inhibition might have no effect on the usage of immune checkpoint inhibitors in lung cancer treatment.
