Author/Editor		Beckhove, Phillip; Fuerer, Markus; Schuetz, Florian; Dolenc, Mathias; Choi, Carmen; Sommerfeldt, Nora; Schwendemann, Jochen; Ehlert, Kathrin; Altevogt, Peter; Bastert, Gunther
Title		Memory T cells as a new tool for tumor immunotherapy
Translated title		Spominske celice T - novo orodje za imunsko zdravljenje tumorjev
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 43, št. Suppl 5
Publication year		2004
Volume		str. 69-73
Language		eng
Abstract		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 autologous dendritic 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.
Summary		V kostnem mozgu večine bolnic z rakom dojke najdemo celice T, ki imajo značilnosti celic s centralnim (angl. central memory - CM) ali efektorskim spominom (angl. effector memory - EM) in ki so specifične za antigene tumorja dojke. Celice T CD8+ iz kostnega mozga in venske krvi bolnic s tumorjem dojke so zmožne specifično vezati HLA/peptidne tetrametre. V poskusu, v katerem smo gojili skupaj bolničine spominske celice T (MTC) iz kostnega mozga in v kratkotrajni kulturi s tumorskim lizatom spodbujene avtologne dendritične celice (DC), so se celice T iz kostnega mozga preoblikovale v učinkovite citotoksične efektorske celice in celice, ki proizvajajo interferon. Da bi preskusili njihovo učinkovitost in vivo, smo osamljene spominske celice T iz kostnega mozga (MTC), ki so bile spodbujene z aktiviranimi dendritičnimi celicami, prenesli v NOD/SCID miši, ki so imele implantirane delčke bolničinega avtolognega tumorja dojke in normalne kožne presadke. MTC, ne pa tudi naivne celice T, so se po prenosu naselile ob tumorskem tkivu, niso pa napadle presajenega normalnega kožnega tkiva. Opisane celice MTC so bile fenotipov CM ali EM in so proizvajale perforin. Mnoge so izražale ligand za P-selektin (P-selektin glikoprotein 1) in so naseljevale področja okoli tumorskega endotelija, ki so bila P-selektin+. Vgnezdene celice MTC in DC so sprožile apoptozo tumorskih celic in povzročile pomembno zmanjšanje tumorjev. Za novo učinkovito zdravljenje raka torej predlagamo skupno uporabo specifično aktiviranih spominskih celic T s centralnim spominom (CM) in efektorskim spominom (EF), skupaj z dendritičnimi celicami (DC).
Descriptors		NEOPLASMS, EXPERIMENTAL IMMUNOTHERAPY T-LYMPHOCYTES ANTIGENS, NEOPLASM MICE BREAST NEOPLASMS