Related Experiment Video
Updated: Aug 14, 2026

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Trans-Presentation of IL-15 by IL15Rα Attenuates Tumor Immune Surveillance and Is Dispensable for IL-15-Dependent
Fjolla Rexhepi1, Sara Ali Akbari1, Mohammad Moradzad2
1Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1H 5H3, Canada.
Background:
IL-15 is a promising cytokine for cancer immunotherapy. IL-15 promotes differentiation and homeostasis of innate and adaptive immune cells, and their cytolytic effector functions. The IL-15 receptor is composed of IL-15Rα, IL-15Rβ and the common γc chains. IL-15 is also trans-presented as IL-15Rα:IL-15 complex to IL-15Rβ:γc on neighboring cells. IL-15Rα is dispensable for early immune response to infections and in autoimmune diabetes. The role of IL-15Rα in antitumor immune responses remains unclear.
Methods:
In WT, Il15-/- and Il15ra-/- mice, we studied the growth of syngeneic tumor cell lines and tumor immune surveillance against endogenous fibrosarcoma induced by methylcholanthrene (MCA). Immune gene signature and total proteome analysis were performed on MCA-induced tumors.
Results:
Lack of IL-15 or IL-15Rα did not enhance the growth of implanted tumor cell lines, despite reduced immune cell infiltration. MCA-induced tumor incidence was reduced in mice lacking IL-15Rα but not IL-15, although both are required for efficient tumor immunoediting. Il15-/- and Il15ra-/- tumors showed reduced Ifng expression but displayed differential modulation of Ifng-responsive genes. Proteome profiles of Il15-/- tumors, but not tumor-derived cell lines, showed significant reduction in antigen presentation pathways. B16-F10 melanoma cells expressing NLRC5, the IFNγ-induced transcriptional activator of tumor antigen presentation, still required IL-15 but not IL-15Rα for efficient tumor control.
Conclusions:
Our findings show that IL-15 plays a negligible role in immunosurveillance against spontaneous tumor development, whereas IL-15Rα restrains immunosurveillance. Neither IL-15 nor IL-15Rα have a significant impact on implanted tumor models, although IL-15 facilitates efficient control of highly immunogenic tumors for which IL-15Rα is dispensable.
Related Concept Videos
Tumor Immunotherapy
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
