Cancer cell targeting by CAR-T cells: A matter of stemness

Chimeric antigen receptor (CAR)-T cell therapy represents one of the most innovative immunotherapy approaches. The encouraging results achieved by CAR-T in hematological disorders paved way for employment CAR engineered T cells different types solid tumors. This adoptive a selective and efficacious approach to eradicate tumors through recognition tumor-associated antigens (TAAs). Binding TAAs provokes release several cytokines, granzyme, perforin that ultimately lead cancer elimination patient’s immune system boosting. Within tumor mass subpopulation cells, known as stem (CSCs), plays crucial role drug resistance, progression, metastasis. has indeed been exploited target CSCs specific an effective strategy heterogeneity disruption. Nevertheless, barrier efficacy cell-based is represented poor persistence into hostile milieu niche, development resistance single targeting antigen, changes metabolism, onset severe adverse effects. corroborated presence immunosuppressive microenvironment (TME), which includes stromal cancer-associated fibroblasts (CAFs), macrophages (TAMs), myeloid-derived suppressor (MDSCs), cells. relationship between TME components dampens therapy. To overcome this challenge, double based on use combination with chemotherapy could be evade TME. Here, we summarize challenges limitations CSCs, particular emphasis metabolic demands.