IL-15 enhances anti-PD-1-induced reinvigoration of tumor-infiltrating CD8+ T cells

• Published in: The Journal of immunology (1950) Vol. 202; no. 1_Supplement; pp. 136 - 136.13
• Main Authors: Leem, Galam, Kim, Kun Woo, Lee, Jea-Ik, Ha, Seung Yeon, Park, Su-Hyung, Kang, Shin Myung, Shin, Eui-Cheol
• Format: Journal Article
• Language: English
• Published: 01.05.2019
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.136.13

Abstract IL-15 is a homeostatic cytokine that induces proliferation of NK cells and memory CD8+ T cells. Recently, clinical trials using various forms of IL-15 in combination with immune checkpoint inhibitors in multiple intractable cancers are on progress. In the present study, we examined effects of IL-15 on tumor-infiltrating CD8+ T cells obtained from human non-small cell lung cancer (NSCLC; n = 20) and synergic effects of IL-15 in combination with anti- PD-1 blocking antibodies. More than 80% of tumor-infiltrating CD8+ T cells expressed PD-1, indicating that they are exhausted. We stimulated tumor-infiltrating CD8+ T cells with anti-CD3 antibodies in the absence or presence of anti-PD-1 blocking antibodies and IL-15 and found that anti-PD-1 treatment increased anti-CD3-stimulated proliferation of tumor-infiltrating CD8+ T cells, indicating that tumor-infiltrating CD8+ T cells were reinvigorated by anti-PD-1. Moreover, IL-15 further enhances anti-PD-1-induced reinvigoration of tumor-infiltrating CD8+ T cells in a dose-dependent manner. These findings indicate that IL-15 might increase therapeutic effects of anti-PD-1 by synergistically enhancing anti-PD-1-induced reinvigoration of tumor-infiltrating CD8+ T cells.