Fig. 2

Possible combination therapies for CAR-T cells. A Combination of CAR-T cells with chemotherapy: Chemotherapy is known to increase the expression of tumor associated antigen (TAA) on cancer cells. This effect will help in (a) enhancing CAR-T cells interaction with cancer cells. Moreover, by downregulating regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs), chemotherapy (b) promotes CAR-T cells proliferation, infiltration and extend their persistence in the TME. These mechanisms strongly support the use of CAR-T cells with chemotherapy for a more potent anti-tumor effect. B Combination of CAR-T cells with oncolytic viruses: Oncolytic viruses promote tumor debulking which (a) enhance CAR-T cells infiltration, proliferation, and activation (b) induce proinflammatory cytokines production, and (c) increase tumor cell death through a double mechanism: direct effect of the virus and enhanced CAR-T cells activity. C Combination of CAR-T cells with radiotherapy: Radiotherapy induces chemokines (CXCLs), interferon-gamma (INF-γ), damage-associated molecular patterns (DAMPs) release by tumor cells leading to (a) increased migration and infiltration of CAR-T cells. Radiotherapy also upregulates TAA expression on tumor cells allowing (b) maturation and activation of dendritic cells associated with better TAA presentation to T cells followed by (c) enhanced CAR-T cells tumor recognition and activation and leading to (d) increased cancer cells death. D Combination of CAR-T cells with immune checkpoint inhibitors (ICIs): ICIs targeting PD1/PDL-1 interaction unleash CAR-T cells inhibition by this repressive pathway. This effect will (a) enhance CAR-T cells cytotoxic activity and consequently (b) promote cancer cell death