Cancer discov: causes of car-t tolerance in cancer cells

February 2, 2020 / biourn / -- in a recent study, researchers at the University of Pennsylvania's Abramson cancer center described how cancer cells' death receptor signaling pathways affect their tolerance to car T cells These findings may provide guidance for the treatment of blood cancer patients with cart The results were published recently in the journal Cancer discovery Car T cell therapy is to target and kill cancer cells in the body by modifying patients' own T cells When these cells are injected into patients, they expand and target cancer cells that express specific receptor proteins About 10% to 20% of patients with acute lymphocytic leukemia (all) have tolerance to car T cells, but up to now, researchers still don't know why (image source: www Pixabay Com) "most theories revolve around T cell defects, but our research shows that the problem lies in the death signaling pathway of cancer cells, which prevents T cells from functioning." Co author Dr Marco ruella said The researchers first screened all cell lines symmetrical as nalm6 based on the whole genome CRISPR / cas9 to isolate the signal pathway related to the production of car t tolerance The team found that in all anti car t treated cells, the activity of genes in the cell death signaling pathway (FADD, bid, CASP8 and tnfrsf10b) decreased, while the genes required in the anti cell death pathway (cflar, TRAF2 and birc2) were highly expressed When they tested this in animal models, it was even more effective than they had observed in vitro Furthermore, the authors found that these mutations in cancer cells lead to the prolongation of cancer cell survival and T cell dysfunction After that, the team analyzed gene expression in leukemic cells and T cells (before and after infusion) from responders and non responders in the patient population They found that in two clinical trials, the signaling pathway of death receptor in cancer cells was directly related to the response to car treatment, further indicating that the signaling pathway of death receptor was a key regulatory factor for the tolerance of all patients to car t treatment Research identified cancer cell defect driving resistance to car T cell therapy original source: Nathan Singh et al Improved death receiver signaling in leukemia causes anti independent resistance by inducing car T cell dysfunction cancer discov January 30 2020 Doi: 10.1158/2159-8290.cd-19-0813