Dendritic cells accelerate CAR T cells in irradiated tumors through chimeric synapses [CITE-seq]

Here we report dramatically enhanced longevity of CAR T cells targeted to irradiated orthotopic lung tumors, leading to durable control in a syngeneic mouse model. CAR T cells robustly infiltrated into irradiated tumors where they maintained elevated expression of cytotoxic effector genes and demonstrated enhanced cytotoxicity.

Remarkably, enhanced CAR T cell persistence in irradiated tumors was critically dependent on dendritic cells through a surprising mechanism. Dendritic cells that underwent “antigen-dressing” of tumor-derived target antigens could activate CAR T cells through the chimeric receptor, while resident and infiltrating myeloid subsets that also underwent antigen-dressing did not, suggesting that DCs were unique amongst myeloid cells in the capacity to maintain CAR T cells.