Immune Regulatory Function of Cancer-Associated Fibroblasts in Non-small Cell Lung Canceropen access
- Authors
- Lee, Hyewon; Hwang, Mina; Jang, Seonae; Um, Sang-Won
- Issue Date
- Oct-2023
- Publisher
- Korean National Tuberculosis Association
- Keywords
- Cancer Associated Fibroblast; COX2; Immune Suppression; PD-L1; Primary Lung Cancer
- Citation
- Tuberculosis and Respiratory Diseases, v.86, no.4, pp 304 - 318
- Pages
- 15
- Indexed
- SCOPUS
ESCI
KCI
- Journal Title
- Tuberculosis and Respiratory Diseases
- Volume
- 86
- Number
- 4
- Start Page
- 304
- End Page
- 318
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/109375
- DOI
- 10.4046/trd.2022.0129
- ISSN
- 1738-3536
2005-6184
- Abstract
- Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors. © 2023 Korean National Tuberculosis Association. All rights reserved.
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