Specific deletion of TGF-β receptor II in macrophages, CD11b⁺Gr1⁺, and dendritic cells inhibit tumor growth by increasing efficiency of the immune system.

By crossing LysM-Cre and TGF-β type II receptor (Tgfbr2) floxed mice we achieved specific deletion of Tgfbr2 in myeloid cells (Tgfbr2^MyeKO mice). S.c.-injected (LLC, EL4-OVA) and implanted (MMTV-PyMT) carcinoma cells grow slower in Tgfbr2^MyeKO mice. The number of CD45⁺ cells in the tumor tissue was the same in both genotypes of mice, but upon analysis, the percentage of T cells (CD45⁺CD3⁺) in the KO mice was increased. By flow cytometry analysis, we did not detect any differences in the number and phenotype of TAMs, CD11b⁺Gr1⁺, and DCs in Tgfbr2^MyeKO compared with Tgfbr2^MyeWT mice. ELISA and qRT-PCR data showed differences in myeloid cell functions. In Tgfbr2^MyeKO TAMs, TNF-α secretion was increased, basal IL-6 secretion was down-regulated, TGF-β did not induce any VEGF response, and there was decreased MMP9 and increased MMP2 and iNOS expression. TGF-β did not have any effect on CD11b⁺Gr1⁺ cells isolated from Tgfbr2^MyeKO mice in the regulation of Arg, iNOS, VEGF, and CXCR4, and moreover, these cells have decreased suppressive activity relative to T cell proliferation. Also, we found that DCs from tumor tissue of Tgfbr2^MyeKO mice have increased antigen-presented properties and an enhanced ability to stimulate antigen-specific T cell proliferation. We conclude that Tgfbr2 in myeloid cells has a negative role in the regulation of anti-tumorigenic functions of these cells, and deletion of this receptor decreases the suppressive function of CD11b⁺Gr1⁺ cells and increases antigen-presenting properties of DCs and anti-tumorigenic properties of TAMs.