B7‐1 and programmed cell death‐ligand 1 in primary and lymph node metastasis lesions of non‐small cell lung carcinoma

• Published in: Cancer medicine (Malden, MA) MA), 2022-01, Vol.11 (2), p.479-491
• Main Authors: Yamada, Takehiro, Miki, Yasuhiro, Suzuki, Miho, Kondoh, Osamu, Saito‐Koyama, Ryoko, Ono, Katsuhiko, Okada, Yoshinori, Sasano, Hironobu
• Format: Article
• Language: English
• Subjects: Aged; Antigens; Apoptosis; B7 antigen; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; B7‐1; Cancer Biology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CD80 antigen; Cell culture; Cell death; Cell Line, Tumor; Dehydrogenases; Female; Genes; Humans; immune check point; Immune checkpoint; Immune Checkpoint Inhibitors - pharmacology; Immunohistochemistry; Kinases; Leukocytes (mononuclear); Ligands; Lung cancer; Lung carcinoma; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; lymph node metastasis; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Lymphocytes; Lymphocytes T; Male; Metastases; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Non-small cell lung carcinoma; non‐small cell lung cancer; PD-L1 protein; PD‐L1; Peripheral blood mononuclear cells; Proteins; Small cell lung carcinoma; Squamous cell carcinoma; Survival Rate; Tumor cell lines; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumor necrosis factor-TNF; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.4444

Background Programmed cell death ligand 1 (PD‐L1) status has been reported to be different between metastatic and primary lesions in some cases. Therefore, the interaction between carcinoma and immune cells could influence their expression in the tumor microenvironment. PD‐L1 is known to bind not only to Programmed cell death 1 (PD‐1) but also to B7‐1 (CD80). In this study, we examined the interaction between lung carcinoma cell lines and peripheral blood mononuclear cells (PBMCs) in vitro. We then examined the significance of B7‐1 expression non‐small cell lung cancer (NSCLC) microenvironment. Methods The interaction of lung carcinoma cell lines and PBMC through the soluble factors was analyzed using a co‐culture system. The changes in expression of immune checkpoint‐related factors in PBMC were examined by PD‐1/PD‐L1 Checkpoint Pathway qPCR Array Kit. B7‐1 expression in NSCLC tissues was examined by immunohistochemistry. Results B7‐1 was upregulated following the co‐culture with the lung carcinoma cell lines. B7‐1 expression in NSCLC tissues was significantly higher in smokers and squamous cell carcinomas and was significantly positively correlated with PD‐L1 status in primary cancer. However, B7‐1 and PD‐1 were not correlated between primary and metastatic diseases in the same patients. Conclusion PD‐1 inhibitors inhibited PD‐1/PD‐L1 binding but not PD‐L1/B7‐1 binding. These results demonstrated that the intratumoral ratio of B7‐1 positive T cells in NSCLC tissue could be involved in the therapeutic efficacy of PD‐L1 inhibitors. This study focused on lymph node metastasis but other sites of distant metastases should be explored by further analysis. Fluorescence microscopic representative illustration of CD4, CD8, and B7‐1 immunohistochemistry.