1255 Modulating phenotypic melanoma heterogeneity and immune cell infiltration

Microphthalmia-associated transcription factor(MITF) is a key player in phenotype switching melanoma. We showed previously that MITF regulates phenotypic melanoma heterogeneity through changing extracellular matrix(ECM) composition and tumor microarchitecture. now hypothesize controls immune cell infiltration changed ECM structure our 3D spheroid model. Our results demonstrate can impact infiltration, yet this dependent on line additional factors, including chemokines cytokines, disease stage (i.e. primary vs. metastatic). To investigate influence from chemokine secretion, we investigated levels the ECM, found MITF-high lines possessed significantly higher IL-8 than MITF-low lines. Notably, peripheral blood mononuclear cells (PBMCs) preferably killed proliferating G1 phase of cycle, whereas G1-arrested escaped surveillance. However, phenomenon appears to be will need tested multiple different stages. Nevertheless, Natural Killer (NK) are likely responsible for elimination, as short duration experiment does not allow T activation. Interestingly, similar elimination was observed when treated with tumor-specific cells. Taken together, firstly reveal correlation between which potentially support predictor clinical outcomes, linked checkpoint inhibitor therapy outcome overall survival patients. Secondly, report first time PBMCs may prefer proliferative phase. This major challenge current treatments, dormant often relapse. Moreover, finding significant beyond melanoma, occurs range solid tumors, prostate, breast, ovarian lung cancer.