IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells.
IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8(+) memory T cell survival and proliferation, IL-15 helps maintain a memory CD8(+) T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8(+) T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8(+) T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8(+) T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.
Klebanoff
Christopher A
CA
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA.
Finkelstein
Steven E
SE
Surman
Deborah R
DR
Lichtman
Michael K
MK
Gattinoni
Luca
L
Theoret
Marc R
MR
Grewal
Navrose
N
Spiess
Paul J
PJ
Antony
Paul A
PA
Palmer
Douglas C
DC
Tagaya
Yutaka
Y
Rosenberg
Steven A
SA
Waldmann
Thomas A
TA
Restifo
Nicholas P
NP
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007167:Immunotherapy; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D058951:gp100 Melanoma Antigen
D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D011948:Receptors, Antigen, T-Cell; D058951:gp100 Melanoma Antigen