Cognate interactions between memory T cells and tumor antigen‐presenting dendritic cells from bone marrow of breast cancer patients: Bidirectional cell stimulation, survival and antitumor activity in vivo

Abstract

Dendritic cells (DC) and T cells were generated from

Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

“…Transfer of sorted, autologous, reactivated BM memory T cells (CD45RA -CD45R0 + ) and DCs led to an infiltration of tumor transplants in NOD/SCID mice by CD4 and CD8 T cells as well as DCs. DCs often colocalized with the T cells and were previously shown to play an important role in this ADI model (30). Infiltration with DCs and CD4 and CD8 T cells was associated with tumor regression and tumor cell destruction in situ, suggesting a possible role of each cell type in tumor regression (30)(31)(32).…”

“…DCs often colocalized with the T cells and were previously shown to play an important role in this ADI model (30). Infiltration with DCs and CD4 and CD8 T cells was associated with tumor regression and tumor cell destruction in situ, suggesting a possible role of each cell type in tumor regression (30)(31)(32). In contrast, enriched naive BM T cells (CD45RA + ), after adoptive transfer, failed to migrate into the tumor area and to cause tumor regression.…”

“…In contrast, enriched naive BM T cells (CD45RA + ), after adoptive transfer, failed to migrate into the tumor area and to cause tumor regression. As no or few T lymphocytes or DCs were observed in patients' tumor specimens growing in control (untreated) mice or in mice treated with sorted re-stimulated naive T cells and DCs, almost all human tumor-infiltrating cells detected in tumor transplants from ADI-treated groups originated from the injected memory T cells that were specifically reactivated by cognate interaction with TA-presenting DCs (30).…”

“…This cytokine plays a major role in the induction and maintenance of Th1 cells, which in contrast to Th2 cells express PSGL1 upon activation (25). We have recently demonstrated a release of high amounts of IL-12 by autologous DCs loaded with Tu-L from breast cancer patients upon cognate interaction in vitro with TA-reactive, IFN-γ-secreting Th1 T cells (19,30). In accordance with this finding, we observed here that more than 30% of adoptively transferred memory T cells infiltrating autologous tumors expressed PSGL1.…”

“…DCs are known to deliver survival signals to T cells especially during cognate interactions (42). We previously reported increased production of IFN-α and IL-15 (which may represent such survival factors) in the supernatants of T cell-DC cocultures upon cognate interaction (30,43). IFN-α induced in DCs by human T cells was shown to be required for IL-12 receptor β expression on human T cells, which then enabled them to respond to IL-12 and to differentiate into Th1 cells (44).…”