Klebanoff Christopher A, Finkelstein Steven E, Surman Deborah R, Lichtman Michael K, Gattinoni Luca, Theoret Marc R, Grewal Navrose, Spiess Paul J, Antony Paul A, Palmer Douglas C, Tagaya Yutaka, Rosenberg Steven A, Waldmann Thomas A, Restifo Nicholas P
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74. doi: 10.1073/pnas.0307298101. Epub 2004 Feb 4.
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.
白细胞介素-15（IL-15）和白细胞介素-2（IL-2）具有相似的特性，包括诱导T细胞增殖的能力。然而，IL-2可促进细胞凋亡并限制CD8(+)记忆性T细胞的存活和增殖，而IL-15则有助于维持记忆性CD8(+) T细胞群体并可抑制细胞凋亡。我们试图通过使用一种T细胞受体转基因小鼠（pmel-1）来确定IL-15是否能够增强肿瘤/自身反应性CD8(+) T细胞的体内功能，该小鼠的CD8(+) T细胞识别源自自身/黑色素瘤抗原gp100的一个表位。通过使用荷瘤IL-15基因敲除宿主去除内源性IL-15，或通过外源给药补充IL-15（作为培养基的一个成分或作为过继转移T细胞所表达的转基因），我们证明IL-15可改善过继转移的CD8(+) T细胞的体内抗肿瘤活性。这些结果为改善癌症患者的过继性免疫治疗提供了多条途径。
