Virus-stimulated neutrophils in the tumor microenvironment enhance T cell-mediated anti-tumor immunity
| Autor: | Chin Yang Chang, Tomoyuki Nishikawa, Sumin Li, Yasufumi Kaneda, Jiayu A. Tai |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Cell Survival Neutrophils T-Lymphocytes Genetic enhancement T cell Chemokine CXCL2 Melanoma Experimental HVJ-E anti-tumor immunity Ligands Sendai virus Mice 03 medical and health sciences 0302 clinical medicine cytotoxic T lymphocytes (CTLs) Cell Line Tumor Tumor Microenvironment medicine Animals Cytotoxic T cell tumor microenvironment (TME) Oncolytic Virotherapy Tumor microenvironment tumor associated neutrophils (TANs) integumentary system biology business.industry Melanoma medicine.disease biology.organism_classification Mice Inbred C57BL CXCL2 Poly I-C 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Immunology Cancer research biology.protein sense organs business Spleen Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Chin Yang Chang 1 , Jiayu A. Tai 1 , Sumin Li 1 , Tomoyuki Nishikawa 1 , Yasufumi Kaneda 1 1 Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan Correspondence to: Yasufumi Kaneda, email: kaneday@gts.med.osaka-u.ac.jp Keywords: HVJ-E, tumor associated neutrophils (TANs), anti-tumor immunity, tumor microenvironment (TME), cytotoxic T lymphocytes (CTLs) Received: November 20, 2015 Accepted: May 22, 2016 Published: May 31, 2016 ABSTRACT The tumor microenvironment (TME) fosters tumors by attenuating anti-tumor immunity, reinforcing tumor cell survival and increasing angiogenesis. Among the constituents of the TME, here, we focused on tumor-associated neutrophils (TANs). First, we found that the combination of poly I:C and inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) synergistically suppressed tumor growth in the B16-F10 melanoma mouse model. In this model, poly I:C contributed to the recruitment of CD11b + Ly6G + neutrophils to the TME, and co-injection of poly I:C and HVJ-E increased CD11b + Ly6G + FAS + TAN in the TME. Depletion of neutrophils abolished the synergistic anti-tumor effect of HVJ-E and poly I:C in B16-F10 tumors. We revealed that C-X-C motif chemokine ligand 2 (CXCL2) is produced in the TME by poly I:C, but HVJ-E enhanced neutrophil infiltration of the TME does not occur. An anti-CXCL2 antibody inhibited the tumor suppression by HVJ-E+poly I:C. HVJ-E in combination with recombinant CXCL2 protein or CXCL2 pDNA suppressed mouse melanoma by increasing cytotoxic T lymphocyte activity against B16-F10 melanoma, which was abolished by an anti-Ly6G antibody. HVJ-E directly and indirectly increased FAS and ICAM-1 expression in cultured bone marrow-derived naive neutrophils. Thus, HVJ-E activates anti-tumor immunity via anti-tumorigenic neutrophils in the TME. An HVJ-E vector containing the CXCL2 gene may be applicable as a novel cancer gene therapy strategy. |
| Databáze: | OpenAIRE |
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