Cytolytic function of NK cells plays an important role to regulate the cancer growth. We hypothesized that inflamed tumor microenvironment regulates the migration of specific subset of NK cells and inhibits their cytolytic function. To investigate the affect of tumor microenvironment on NK cell migration and function, B16F10 melanoma cells (1 X 106 cells/mouse) were injected (s.c.) into C57BL/6 mice. Depletion of NK cells showed 3-4 fold increased tumor growth compared to control IgG treated mice. Tumor transplanted (day 10) and naïve mice did not showed any significant difference in percentage and absolute number of CD11b+CD27+, CD11b+CD27- or CD11b-CD27+ NK cells in spleen and lymph nodes. However, CD11b+CD27+CD3-NK1.1+ cells were selectively recruited into the tumor. At day 5, increase CD31+ endothelial cell staining were observed. qRT-PCR analysis of tumor associated endothelial cells (CD31+CD45- cells) showed increased CCL2, CCL21, CXCL10, and CXCL12 mRNA expression compared to splenic blood endothelial cells. Tumor infiltrating NK cells (day 13) showed increased expression of CCR2, CXCR4, IL-6, FasL mRNA expression, and decreased perforin, IFNg and IL-21 expression compared to splenic NK subsets. These results demonstrate that inflamed tumor microenvironment selectively recruits a specific subset of NK cell and inhibit their cytolytic function. This suggests that modulating tumor microenvironment may be key to boost the NK cell function to control cancer progression.
- Copyright © 2013 by The American Association of Immunologists, Inc.