Barbera et al. showed that T cells reciprocally transferred CARs and TCRs via trogocytosis in vitro and in mouse models. T cell activation boosted trogocytosis. CAR transfer to T, B, and NK cells was detected in the TME and occurred at higher levels when tumors expressed cognate antigen. T cells that trogocytosed CARs or TCRs were activated by and lysed specific tumor cells. Trogocytosis was controlled by a protein’s TM domain, and required cell–cell contact, but not a cognate binding partner on the recipient cells’ membrane. The probability of trogocytosis correlated with protein positioning in microvilli at the donor–recipient T cell interface.
Contributed by Paula Hochman
ABSTRACT: Trogocytosis is an exchange of membrane-associated molecules between cells that can either halt or boost immune responses. However, the mechanism that regulates trogocytosis in T cells and its consequences are not yet clear. Here, we demonstrate that T cells can exchange chimeric antigen receptors (CARs) by trogocytosis, thereby arming recipient T cells with the capacity to respond to tumor antigens by up-regulating proteins associated with a cytotoxic response and killing of target cells. We demonstrate that although trogocytosis is dependent on cell-cell contact, the exchange of a specific cell membrane protein does not require a cognate binding partner on the surface of recipient cells. Instead, the probability that a protein is exchanged by trogocytosis is determined by its transmembrane domain. This finding opens new avenues for modulating this process in CAR-T cells.
Author Info: (1) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (2) Department of Immunology, Genetics and Pathology, Scienc
Author Info: (1) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (2) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (3) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (4) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (5) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (6) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (7) Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
