Shift from systemic to site-specific memory by tumor-targeted IL-2.
IL-2 has been approved for treatment of patients with cancer. Moreover, it has been used as a component of vaccines against cancer. In this regard, we have recently demonstrated that dendritic cell-based peptide vaccination in mice required IL-2 to mount an effective immune response against established melanoma metastases. In this study, we confirm this observation by use of tumor-targeted IL-2. However, the development of a protective systemic memory was substantially impaired by this measure, i.e., mice, which successfully rejected s.c. tumors of B16 melanoma after vaccination with dendritic cells pulsed with tyrosinase-related protein 2-derived peptides plus a boost with targeted IL-2, failed to reject a rechallenge with experimental pulmonary metastases. Detailed analysis revealed a change in the distribution of the tumor-reactive T cell population: although targeted IL-2 expanded the local effector population, tyrosinase-related protein 2-reactive T cells were almost completely depleted from lymphatic tissues.
Schrama
David
D
Department of Dermatology, Julius-Maximilians University, Würzburg, Germany.
Xiang
Rong
R
Eggert
Andreas O
AO
Andersen
Mads Hald
MH
Pedersen Ls
Lars Østergaard
LØ
Kämpgen
Eckhart
E
Schumacher
Ton N
TN
Reisfeld
Ralph R
RR
Becker
Jürgen C
JC
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
D006131:Growth Inhibitors; D007376:Interleukin-2; D022223:Vaccines, Subunit; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase