Spominske celice T - novo orodje za imunsko zdravljenje tumorjev = Memory T cells as a new tool for tumor immunotherapy
Beckhove, Phillip
Bone marrow (BM) of most breast cancer patients contains T cells with central (CM) or effector memory (EM) phenotype and specificity for breast tumor antigens (TA). CD8+ T cells from patients' BM and ...peripheral blood (PB) specifically bind HLA/peptide tetramers. In short-term culture with autologousdendritic cells (DC) pulsed with tumor lysate, patients' memory T cells (MTC) from BM (but not PB) can be reactivated to interferon (IFN)-gamma producing and cytotoxic effector cells. To test their in vivo function, separated BM MTC or naive cells were stimulated with TA-pulsed DC and transferred into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. MTC but not naive T cells infiltrated tumor but not skin tissues after the transfer. These cells had CM or EM phenotype and produced perforin. Many of them expressed a ligand for P-selectin (P-selectin glycoprotein 1) and were found around P-selectin' tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by MTC and DC and was associated with tumor cell apoptosis and significant tumor reduction. We suggest that specifically activated CM and EM T cells, which can be applied together with DC, should be used for novel effective cancer therapy.
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