Tumor-associated macrophages induce PD-L1 expression in gastric cancer cells through IL-6 and TNF-ɑ signaling
Copyright © 2020 Elsevier Inc. All rights reserved..
PD-1/PD-L1 immune checkpoint blockade therapy has been widely used for the clinical treatment of cancer. However, recent clinical trials have shown that only a small proportion of cancer patients respond to PD1/PD-L1 immunotherapy. The tumor immune microenvironment plays an important regulatory role in PD1/PD-L1 immunotherapy. Macrophages are one of the most important immune cells in the tumor immune microenvironment. In this study, we found a high correlation between macrophage infiltration and PD-L1 expression in gastric cancer (GC) specimens. Further study revealed that infiltrated macrophages released the proinflammatory cytokines TNF-ɑ and IL-6, which induced PD-L1 expression in tumor cells. The release of TNF-ɑ and IL-6 activated the NF-kB and STAT3 signaling pathway to regulate PD-L1 expression. TNF-α, p-65 and STAT3 expression in cancer patients has prognostic value in stomach adenocarcinoma. Furthermore, infiltrated macrophages can also promote GC cell proliferation by inducing PD-L1 expression in GC cells. Taken together, our results suggest that macrophages play a dual role in regulating the expression of PD-L1 in tumor cells. On the one hand, macrophages induce PD-L1 expression in tumor cells, helping tumor cells escape cytotoxic T cell killing; on the other hand, they can promote the proliferation of tumor cells by regulating the expression of PD-L1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:396 |
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| Enthalten in: |
Experimental cell research - 396(2020), 2 vom: 15. Nov., Seite 112315 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ju, Xiaoli [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.03.2021 Date Revised 09.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.yexcr.2020.112315 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316018449 |
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| 245 | 1 | 0 | |a Tumor-associated macrophages induce PD-L1 expression in gastric cancer cells through IL-6 and TNF-ɑ signaling |
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| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a PD-1/PD-L1 immune checkpoint blockade therapy has been widely used for the clinical treatment of cancer. However, recent clinical trials have shown that only a small proportion of cancer patients respond to PD1/PD-L1 immunotherapy. The tumor immune microenvironment plays an important regulatory role in PD1/PD-L1 immunotherapy. Macrophages are one of the most important immune cells in the tumor immune microenvironment. In this study, we found a high correlation between macrophage infiltration and PD-L1 expression in gastric cancer (GC) specimens. Further study revealed that infiltrated macrophages released the proinflammatory cytokines TNF-ɑ and IL-6, which induced PD-L1 expression in tumor cells. The release of TNF-ɑ and IL-6 activated the NF-kB and STAT3 signaling pathway to regulate PD-L1 expression. TNF-α, p-65 and STAT3 expression in cancer patients has prognostic value in stomach adenocarcinoma. Furthermore, infiltrated macrophages can also promote GC cell proliferation by inducing PD-L1 expression in GC cells. Taken together, our results suggest that macrophages play a dual role in regulating the expression of PD-L1 in tumor cells. On the one hand, macrophages induce PD-L1 expression in tumor cells, helping tumor cells escape cytotoxic T cell killing; on the other hand, they can promote the proliferation of tumor cells by regulating the expression of PD-L1 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Infiltrated macrophages | |
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| 700 | 1 | |a Zhou, Zidi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qiang |e verfasserin |4 aut | |
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