Joining Forces: Improving Clinical Response to Cellular Immunotherapies with Small-Molecule Inhibitors

Adoptive T cell therapy (ACT) has emerged as a powerful therapeutic tool against both hematological and virus-associated cancers. However, extension of this success to solid cancers has been challenging owing to intratumoral mechanisms that induce a hostile immunosuppressive tumor microenvironment (TME). Delineating the impact of tumor-intrinsic adaptive resistance mechanisms on immune-based therapies is essential to improve long-term efficacy. We discuss the different tumor-intrinsic factors that lead to resistance to ACT. We highlight the potential of repurposing molecular targeted therapies to modulate immune responses and override intratumor resistance to ACT. Finally, we discuss the potential of combining targeted therapy and ACT as a new paradigm to improve the clinical efficacy of cancer therapeutics