Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10.
J Immunother Cancer
BACKGROUND: Interleukin-15 (IL-15) promotes growth and activation of cytotoxic CD8
METHODS: The antitumor activity of hetIL-15 produced from mammalian cells was tested in mouse tumor models (MC38 colon carcinoma and TC-1 epithelial carcinoma). The functional diversity of the immune infiltrate and the cytokine/chemokine network within the tumor was evaluated by flow cytometry, multicolor immunohistochemistry (IHC), gene expression profiling by Nanostring Technologies, and protein analysis by electrochemiluminescence and ELISA assays.
RESULTS: hetIL-15 treatment resulted in delayed primary tumor growth. Increased NK and CD8
CONCLUSIONS: Our results show that hetIL-15 administration enhances T cell entry into tumors, increasing the success rate of immunotherapy interventions. Our study further supports the incorporation of hetIL-15 in tumor immunotherapy approaches to promote the development of antitumor responses by favoring effector over regulatory cells and by promoting lymphocyte and DC localization into tumors through the modification of the tumor chemokine and cytokine milieu.
Earle A. Chiles Research Institute
Bergamaschi, Cristina; Pandit, Hrishikesh; Nagy, Bethany A; Stellas, Dimitris; Jensen, Shawn M.; Bear, Jenifer; Cam, Maggie; Valentin, Antonio; Fox, Bernard A; Felber, Barbara K; and Pavlakis, George N, "Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10." (2020). Articles, Abstracts, and Reports. 3198.