Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition

Abstract

Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response. Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is ex vivo cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations. We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties. Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.