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Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype
Ist Teil von
Frontiers in immunology, 2020-12, Vol.11, p.594775-594775
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2020
Link zum Volltext
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15
CD163
TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15
CD163
macrophages inhibited antitumor CD8
cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.