Tnfα Expression by Myeloid Cells in Ascites Regulate Colorectal Cancer

Abstract

Abstract

Objectives: CD14+ macrophages within a tumor or in peripheral blood (PB) are cytotoxic during the early stages but support cancer cell proliferation in the late stages. We investigated the role of inflammatory cells in ascites in patients with colorectal cancer (CRC).

Methods: We prospectively enrolled 18 consecutive patients with CRC and 5 patients with inguinal hernia (IH) requiring laparoscopic approach. Inflammatory cells in the peritoneal fluid were enumerated. To investigate the function of the major fraction, we collected CD45+ and CD14+ cells (approximately 5 × 10⁵ cells) by fluorescence-activated cell sorting and analyzed CD14+ cells in ascites and PB using M1 (TNFα, iNOS, and CCR2) and M2 markers (ARG1, IL-10, and TGF- β). HCT116 cells (colon cancer) were co-cultured with CD14+ macrophages from ascites and PB from patients to investigate cancer cell proliferation.

Results: There were no significant differences in CD14+ cell numbers (mean, 5.5 vs. 10.1%) in the peritoneal fluid of the two groups, but TNFα levels in CRC ascites macrophages were significantly higher than those from PB of IH (p < 0.01). CD14+ cells from ascites of patients with CRC better suppressed cancer cell proliferation (p < 0.01), but cancer cell proliferation persisted in the presence of TNFα antibodies (p < 0.01).

Conclusions: Myeloid-derived CD14+ cells in the environment of ascites can infiltrate in tumors of patients with CRC; they appear to be M1 macrophages, and expression of TNFα can suppress the growth of CRC cells.