Tumor-derived exosomes induce PD1+ macrophage population in human gastric cancer that promotes disease progression

Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutive...

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Veröffentlicht in:Oncogenesis (New York, NY) Jg. 7; H. 5; S. 41 - 11
Hauptverfasser: Wang, Furong, Li, Bin, Wei, Yucai, Zhao, Yang, Wang, Li, Zhang, Peng, Yang, Jinwei, He, Wenting, Chen, Hao, Jiao, Zuoyi, Li, Yumin
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 25.05.2018
Nature Publishing Group
Schlagworte:
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Angiogenesis
Apoptosis
CD8 antigen
Cell Biology
Cell death
Chemokines
Exosomes
Gastric cancer
Human Genetics
Immune response
Immunosuppressive agents
Immunotherapy
Interleukin 10
Interleukin 12
Internal Medicine
Lymphocytes T
Macrophages
Major histocompatibility complex
Medicine
Medicine & Public Health
Metastases
Monocytes
Oncology
Ovalbumin
PD-1 protein
Phenotypes
Recovery of function
T cell receptors
Tumor-infiltrating lymphocytes
ISSN:2157-9024, 2157-9024
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Zusammenfassung:Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1 + tumor-associated macrophages (TAMs) exhibited an M2-like surface profile, with a significant increase in the expression of CD206, IL-10, and CCL1, and a clear decrease in the expression of MHC class II, CD64, and IL-12 and the ability to phagocytose ovalbumin. Moreover, PD1 + TAMs can suppress CD8 + T-cell function and this immunosuppressive activity can effectively be enhanced upon triggering PD1 signal. GC-derived exosomes effectively educated monocytes to differentiate into PD1 + TAMs with M2 phenotypic and functional characteristics. Together, our results are the first to show that GC-derived exosomes can effectively induce PD1 + TAM generation, and these cells can produce a large number of IL-10, impair CD8 + T-cell function, and thereby create conditions that promote GC progression. Thus, methods in which immunotherapy is combined with targeting PD1 + TAMs and tumor-derived exosomes should be used to restore immune function in GC patients.
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ISSN:2157-9024
2157-9024
DOI:10.1038/s41389-018-0049-3