Interaction Between Mesenchymal Stromal Cells and Tumor Cells Present in Cervical Cancer Influences Macrophage Polarization

Background/Objectives: Macrophages with the M2 phenotype are an immune population with great relevance for tumor development. We have previously demonstrated that mesenchymal stromal cells (MSCs) from cervical cancer (CeCa-MSCs) enhance the immunomodulatory activity of CeCa cells on T lymphocytes; however, the effect of these cells on the ability of tumor cells to polarize macrophages had not been evaluated to date. Methods: To address this, we set out to analyze the effect of normal cervix (NCx) and CeCa-MSCs interacting with CeCa tumor cells (TCs) to polarize macrophages in a coculture system. Results: Our results show that macrophages from TC/NCx-MSC cocultures decreased CD163 expression. In turn, we observed that macrophages from TC/CeCa-MSC cocultures, in contrast to those in the presence of TCs/NCx-MSCs, increased the intracellular production of IDO, IL-4, and IL-10; decreased T lymphocyte proliferation; and increased the presence of soluble IL-10. Interestingly, coculture in the presence of TCs/NCx-MSCs decreased the capacity of macrophages to generate regulatory T lymphocyte populations, as well as their phagocytic capacity, and increased IL-6 secretion, unlike the coculture of macrophages in the presence of TCs/CeCa-MSCs. Our results show that TCs/CeCa-MSCs in cocultures, unlike TCs/NCx-MSCs, have a greater capacity to polarize macrophages to an M2 phenotype and that such macrophages have a greater immunosuppressive potential. Conclusions: This in vitro study suggests that intracellular communication between MSCs and tumor cells in CeCa may promote tumor growth through the polarization of macrophages with increased immunosuppressive activity.