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.

Publication Title

J Immunother Cancer

Authors

Cristina Bergamaschi
Hrishikesh Pandit
Bethany A Nagy
Dimitris Stellas
Shawn M. Jensen, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center and Providence Portland Medical Center, Portland, OregonFollow
Jenifer Bear
Maggie Cam
Antonio Valentin
Bernard A Fox, Chiles Research Institute Providence Portland Medical CenterFollow
Barbara K Felber
George N Pavlakis

Document Type

Article

Publication Date

5-1-2020

Abstract

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.

Clinical Institute

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Earle A. Chiles Research Institute