Infiltration of folate receptor-expressing immune cells into the tumor microenvironment and chemotherapy resistance

Myeloid cells have a crucial role in the development, progression, metastasis, and resistance mechanisms of breast cancer. The study comprises two primary objectives: i. to investigate the systemic effects of myeloid cells in the tumor microenvironment and different organs, depending on time during breast cancer. ii. to examine the distribution of myeloid cells in tumor and metastatic lung tissues, as well as the changes in microenvironment dynamics induced by chemotherapy in the development of breast cancer based on P-gp expression. Upon evaluating the infiltration of myeloid cells in the tumor tissue depending on time, it was observed that macrophage populations were the most important population at all phases. FRβ expression in CD206+ macrophages, which promote immune suppression, significantly increased in the later phase. In the EMT6/AR1 tumor model, CD206+FRβ+ macrophages significantly increased in the early phase of tumor development compared to the EMT6 model. In the late stage, it is observed that CD206+FRβ+ macrophages decreased. In groups administered early-stage chemotherapy, an increase in CD206+FRβ+ macrophages in the tumor was observed in the DOX treatment groups compared to other treatment groups, regardless of the tumor model. The number of alveolar macrophages in the lung tissue was dramatically decreased. In groups treated late chemotherapy, monocyte infiltration the lung decreased in the EMT6 model compared to the control group, whereas it increased in the EMT6/AR1 model. Regardless of the chemotherapy application, the difference in monocyte infiltration in tumor models with different P-gp expressions was found to be significant.