A tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses

T cells to overcome checkpoint blockade resistance. Moreover, pro-IL-15 promotes chemotaxis and activation of adoptive T cells, leading to eradication of advanced solid tumors and durable cures. Furthermore, pro-IL-15 shows promise for synergizing with other immunotherapies like IL-12 and oncolytic virus by improving the CD8/Treg ratio and interferon-γ levels, resulting in substantial regression of both local and metastatic cold tumors. Collectively, our results suggest that pro-IL-15 represents a compelling strategy for overcoming resistance to current immunotherapies while avoiding toxicities.