The Engelsen group is dedicated to exploring how phenotypic plasticity interferes with therapeutic efficacy and immune cell-mediated killing.
The Engelsen group is dedicated to exploring how phenotypic plasticity interferes with therapeutic efficacy and immune cell-mediated killing. Through national and international collaborations, the group aims to unravel the best molecular targets to prevent phenotypic plasticity-driven therapy resistance and immune escape in solid tumors and to contribute to the design of better predictive tools for
The group has recently established a local interdisciplinary collaboration that allows them to generate benign and non-small cell lung cancer (NSCLC) patient-derived organoids and explant cultures from lobectomy specimens (Hoareau et al., 2021, Ekanger et al., 2022), working on characterizing how well the models preserve the various NSCLC histological subtypes.
Hypoxia is a major driver of an aggressive and immune evasive tumor microenvironments (Zaarour et al., 2021, Engelsen et al., 2022). In one subproject, the group explores how hyperbaric oxygen therapy may be applied to improve the efficacy of immune checkpoint inhibition by modulating the metabolism of and the crosstalk between malignant cells and cells of the tumor immune microenvironment.
The group has shown how intrinsic differences in spatiotemporal organization and stromal cell interactions between isogenic lung cancer cells of epithelial and mesenchymal phenotypes can be revealed by high-dimensional single-cell analysis of heterotypic 3D spheroid models (Lotsberg et al., Front Oncol, 2022). This project serves as an important technical achievement for the group, and the study supports further applications of their complementary models in preclinical drug testing combined with high-dimensional single-cell analysis. This combination is expected to reveal cancer-stroma interactions and advance the understanding on the impact of epithelial phenotypic plasticity on innate and acquired therapy resistance in NSCLC.
The NSCLC explant models recapitulate the complex tumorimmune microenvironment, and current projects aim to elucidate the effect of phenotypic plasticity on the spatial organization of the tumor immune microenvironment and explore how therapeutic targeting of phenotypic plasticity synergize with immune checkpoint inhibition (ICI) therapy, which serves to release the brakes that cancer cells can put on the immune system.