期刊
ONCOIMMUNOLOGY
卷 7, 期 3, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1393598
关键词
CCL3; natural killer cells; CD8(+) T cells; CD103(+) dendritic cells; interferon-gamma; CXCL9; CXCL10
资金
- National Institutes of Health [R01CA154656, R21CA181875, R21CA218790, R01HL111682, P30CA043703]
- NCI [R01CA154656-S1, F31CA192874, R01AI091627]
- Rainbow Foundation at UH Rainbow Babies & Children's Hospital
- St. Baldrick's Foundation
- Alex's Lemonade Stand Foundation
- Hyundai Hope-on-Wheels Program
- Pediatric Cancer Research Foundation
- Steven G. AYA Cancer Research Fund
- Samuel Szabo Foundation
- Keira Kilbane Cancer Discovery Fund
- Errol's Cancer Discovery Fund
- Risman Family Philanthropic Funds
- Cleveland Foundation
- Harrington Discovery Institute
- Theresia G. & Stuart F. Kline Family Foundation
- NATIONAL CANCER INSTITUTE [R21CA181875] Funding Source: NIH RePORTER
Inflammatory chemokines are critical contributors in attracting relevant immune cells to the tumor microenvironment and driving cellular interactions and molecular signaling cascades that dictate the ultimate outcome of host anti-tumor immune response. Therefore, rational application of chemokines in a spatial-temporal dependent manner may constitute an attractive adjuvant in immunotherapeutic approaches against cancer. Existing data suggest that the macrophage inflammatory protein (MIP)-1 family and related proteins, consisting of CCL3 (MIP-1), CCL4 (MIP-1), and CCL5 (RANTES), can be major determinant of immune cellular infiltration in certain tumors through their direct recruitment of antigen presenting cells, including dendritic cells (DCs) to the tumor site. In this study, we examined how CCL3 in a murine colon tumor microenvironment, CT26, enhances antitumor immunity. We identified natural killer (NK) cells as a major lymphocyte subtype that is preferentially recruited to the CCL3-rich tumor site. NK cells contribute to the overall IFN content, CD103(+) DC accumulation, and augment the production of chemokines CXCL9 and CXCL10 for enhanced T cell recruitment. We further demonstrate that both soluble CCL3 and CCL3-secreting irradiated tumor vaccine can effectively halt the progression of established tumors in a spatial-dependent manner. Our finding implies an important contribution of NK in the CCL3 - CD103(+) DC - CXCL9/10 signaling axis in determining tumor immune landscape within the tumor microenvironment.
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