Dermal wounds alter tumor immunobiology in mice

Abstract

Tumor growth, angiogenesis, and invasion are modulated by tumor-infiltrating myeloid cells. The production of these cells by the bone marrow is an energetically-costly process, and therefore, finite and tightly regulated. Both prophylactic (e.g., biopsy) and direct cancer treatment (e.g., tumor surgery) require often elaborate skin wound healing, another myeloid cell-recruiting process. Thus, we tested the hypothesis that dermal wound healing depletes tumors of some myeloid cell populations, thereby affecting tumor immunobiology, and ultimately, increases tumor growth. Oral cancer cells (106) or PBS were injected (s.c.) into the flank of adult female immunocompetent C3H mice. Sixteen days post-tumor induction, two 3.5 mm excisional wounds were placed through the dorsal skin; other mice remained unwounded. Blood, wounds, bone marrow, spleen, tumor, and tumor-draining lymph nodes were collected 1 or 5 days later. In mice that were wounded, tumor mass modestly increased five days after wounding. The numbers of circulating leukocytes were not significantly affected by wounding; however, tumors increased the percentages of neutrophils and monocytes and decreased lymphocytes. Tumor gene expression of various inflammatory markers (CCL2, CXC10, IL-6, Tnfalpha, MIP-1) was modulated by whether or not a wound was also present. Flow cytometry will determine immune cell trafficking throughout the body. The goal of this work is to provide an understanding of how standard clinical treatments affect tumor immunobiology, and therefore, tumor growth and metastases.