Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Research Année : 2008

Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells

Résumé

Tumors often escape immune-mediated destruction by suppressing lymphocyte infiltration or effector function. New approaches are needed that overcome this suppression and thereby augment the tumoricidal capacity of tumor-reactive lymphocytes. The cytokine interleukin-15 (IL-15) promotes proliferation and effector capacity of CD8(+) T cells, natural killer (NK) cells, and NKT cells; however, it has a short half-life and high doses are needed to achieve functional responses in vivo. The biological activity of IL-15 can be dramatically increased by complexing this cytokine to its soluble receptor, IL-15R alpha. Here, we report that in vivo delivery of IL-15/IL-15R alpha complexes triggers rapid and significant regression of established solid tumors in two murine models. Despite a marked expansion of IL-2/IL-15R beta(+) cells in lymphoid organs and peripheral blood following treatment with IL-15/IL-15R alpha complexes, the destruction of solid tumors was orchestrated by tumor-resident rather than newly infiltrating CD8(+) T cells. Our data provide novel insights into the use of IL-15/IL-15R alpha complexes to relieve tumor-resident T cells from functional suppression by the tumor microenvironment and have significant implications for cancer immunotherapy and treatment of chronic infections.

Dates et versions

hal-01602340 , version 1 (02-10-2017)

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Citer

Mathieu Epardaud, Kutlu G. Elpek, Mark P. Rubinstein, Ai-Ris Yonekura, Angélique Bellemare-Pelletier, et al.. Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Research, 2008, 68 (8), pp.2972-2983. ⟨10.1158/0008-5472.CAN-08-0045⟩. ⟨hal-01602340⟩
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