Fig. 1

a. Lymphodepleting chemotherapy reduces the number of suppressive cells, such as regulatory T cells and type 2 helper cells, which can disturb the tumor microenvironment. It also stimulates production of cytokines, such as IL-7 and IL-15, which can promote expansion of CAR-T cells. b. Hodgkin Reed-Sternberg cells produce thymus and activation-regulated chemokine/CC chemokine ligand 17 (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), which attract type 2 helper cells and regulatory T cells that express CCR4. CAR-T cells that are engineered to express CCR4 may have improved trafficking to the tumor site. c. Anti-CD30 CAR-T cells have been found to express PD-1, which suggests that they may be susceptible to the PD-1/PD-L1 pathway that leads to immune inhibition. In addition, Hodgkin Reed-Sternberg cells also express PD-L1, which may have an inhibitory effect on CAR-T cells expressing PD-1. Checkpoint inhibitors can interrupt the PD-1/PD-L1 pathway and lead to improved expansion and persistence of CAR-T cells. Growth factors, such as colony-stimulating factor 1 (CSF1) stimulate tumor associated macrophages (TAM) to be anti-inflammatory and promote tumor development. Combinations with CSF1 receptor (CSF1R) inhibitors could help interrupt the inhibitory tumor microenvironment and improve CAR-T cell efficacy