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

P Beckhove, M Feuerer, M Dolenc… - The Journal of …, 2004 - Am Soc Clin Investig
P Beckhove, M Feuerer, M Dolenc, F Schuetz, C Choi, N Sommerfeldt, J Schwendemann…
The Journal of clinical investigation, 2004Am Soc Clin Investig
Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for
peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of
these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–
CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived
CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous
dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing …
Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RACD62L+ or CD45RACD62L, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RACD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.
The Journal of Clinical Investigation