PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells
Cancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Coh...
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1257 |
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| author | Chihiro Inoue Yasuhiro Miki Ryoko Saito Shuko Hata Jiro Abe Ikuro Sato Yoshinori Okada Hironobu Sasano |
| author_facet | Chihiro Inoue Yasuhiro Miki Ryoko Saito Shuko Hata Jiro Abe Ikuro Sato Yoshinori Okada Hironobu Sasano |
| author_sort | Chihiro Inoue |
| collection | DOAJ |
| description | Cancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Cohorts 1 and 2, respectively. The patients in Cohort 1 received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrent lung adenocarcinoma. α-smooth muscle actin (α-SMA), a surrogate marker for CAFs, was examined by immunohistochemistry. We then examined the effects of CAFs isolated from lung cancer tissues on programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma cell lines. No significant associations were detected between α-SMA status and the ratios of CD8/CD4 and Foxp3/CD8 in Cohort 1. However, α-SMA status was significantly associated with PD-L1 status in both Cohorts 1 and 2. Conditioned medium of CAFs significantly induced PD-L1 expression in lung adenocarcinoma cell lines, A549, PC-9, and H1975. Among the cytokines examined by antibody array, C-X-C motif chemokine ligand 2 (CXCL2) increased PD-L1 mRNA expression in these cell lines. CXCL2 is therefore considered to have a potential to induce PD-L1 expression in lung adenocarcinoma cells as a result of an interaction between carcinoma cells and CAFs. These findings did firstly demonstrate that CAFs indirectly influenced tumour immunity through increasing PD-L1 expression in lung adenocarcinoma cells. |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:51:56Z |
| publishDate | 2019-08-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-178b21fd20ab47c9a9c6f5a1ab93b2202023-09-02T12:28:12ZengMDPI AGCancers2072-66942019-08-01119125710.3390/cancers11091257cancers11091257PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma CellsChihiro Inoue0Yasuhiro Miki1Ryoko Saito2Shuko Hata3Jiro Abe4Ikuro Sato5Yoshinori Okada6Hironobu Sasano7Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 981-8575, JapanDepartment of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University, Sendai, Miyagi 980-8573, JapanDepartment of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 981-8575, JapanDivision of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, JapanDepartment of Thoracic Surgery, Miyagi Cancer Centre, Natori, Miyagi 981-1293, JapanDepartment of Pathology, Miyagi Cancer Centre, Natori, Miyagi 981-1293, JapanDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 981-8575, JapanDepartment of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 981-8575, JapanCancer-associated fibroblasts (CAFs) exert various effects upon biological behaviours of cancer. In this study, we examined the correlation of CAFs with the intra-tumoural immune system in the lung adenocarcinoma microenvironment. We studied 27 and 113 cases of lung adenocarcinoma tentatively as Cohorts 1 and 2, respectively. The patients in Cohort 1 received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrent lung adenocarcinoma. α-smooth muscle actin (α-SMA), a surrogate marker for CAFs, was examined by immunohistochemistry. We then examined the effects of CAFs isolated from lung cancer tissues on programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma cell lines. No significant associations were detected between α-SMA status and the ratios of CD8/CD4 and Foxp3/CD8 in Cohort 1. However, α-SMA status was significantly associated with PD-L1 status in both Cohorts 1 and 2. Conditioned medium of CAFs significantly induced PD-L1 expression in lung adenocarcinoma cell lines, A549, PC-9, and H1975. Among the cytokines examined by antibody array, C-X-C motif chemokine ligand 2 (CXCL2) increased PD-L1 mRNA expression in these cell lines. CXCL2 is therefore considered to have a potential to induce PD-L1 expression in lung adenocarcinoma cells as a result of an interaction between carcinoma cells and CAFs. These findings did firstly demonstrate that CAFs indirectly influenced tumour immunity through increasing PD-L1 expression in lung adenocarcinoma cells.https://www.mdpi.com/2072-6694/11/9/1257cancer associated fibroblaststumor microenvironmentα-smooth muscle actinprogrammed death ligand 1lung adenocarcinoma |
| spellingShingle | Chihiro Inoue Yasuhiro Miki Ryoko Saito Shuko Hata Jiro Abe Ikuro Sato Yoshinori Okada Hironobu Sasano PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells Cancers cancer associated fibroblasts tumor microenvironment α-smooth muscle actin programmed death ligand 1 lung adenocarcinoma |
| title | PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells |
| title_full | PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells |
| title_fullStr | PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells |
| title_full_unstemmed | PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells |
| title_short | PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells |
| title_sort | pd l1 induction by cancer associated fibroblast derived factors in lung adenocarcinoma cells |
| topic | cancer associated fibroblasts tumor microenvironment α-smooth muscle actin programmed death ligand 1 lung adenocarcinoma |
| url | https://www.mdpi.com/2072-6694/11/9/1257 |
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