Interleukin-21 restrains tumor growth and induces a substantial increase in the number of circulating tumor-specific T cells in a murine model of malignant melanoma.
New strategies of immunotherapy are currently being evaluated, and the combination of chemo- and immunotherapy has shown promising results. The cytokine interleukin-21 (IL-21) is known to enhance immune function, and in this study we have investigated its ability to boost the efficacy of chemoimmunotherapy-cyclophosphamide and adoptive cell transfer (ACT)-in the B16-OVA/OT-I murine model of malignant melanoma. Subcutaneous B16-OVA tumors were established in C57BL/6J mice 8 days before adoptive transfer of tumor-specific OT-I T cells. In addition to cyclophosphamide and ACT, one group of mice received daily injections of murine IL-21 (mIL-21). Mice treated with mIL-21 had more tumor-specific T cells in the circulation 4 and 7 days following ACT (P=0.004 and P=0.002, respectively). Importantly, mIL-21 and ACT controlled tumor growth instantly and more effectively than ACT alone (P=0.001, day 4)-an effect that persisted up to 5 days after the last mIL-21 injection. We conclude that mIL-21 enhances chemoimmunotherapy: it amplifies the number of tumor-specific T cells in the circulation and also stunts early tumor growth.
Petersen
Charlotte Christie
CC
Institute of Medical Microbiology and Immunology, Aarhus University, DK-8000 Aarhus C, Denmark. ccp@immunology.au.dk
Diernaes
Jon Erik Fraes
JE
Skovbo
Anni
A
Hvid
Malene
M
Deleuran
Bent
B
Hokland
Marianne
M
D019264:Adoptive Transfer; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy / Q000379:methods; D007378:Interleukins / Q000276:immunology / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D000098546:Interleukin-21; D052118:Lysosomal-Associated Membrane Protein 1
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D007378:Interleukins; D051907:Lysosomal Membrane Proteins; D000098546:Interleukin-21; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1