| The prognosis of many patients with cancer has been markedly improved with treatment with checkpoint inhibitors, including patients with head and neck squamous cell carcinoma (HNSCC); however, the treatment is not effective long term and many patients relapse. One approach that may improve the use of checkpoint inhibitors is the addition of IL-15 during treatment with checkpoint inhibitors. IL-15 is an important gamma (gamma)C-cytokine that plays a crucial role in multiple innate and adaptive immune responses to tumors and is important for the survival of memory CD8+ T cells, which are critical for the rejection of solid tumors and maintaining durable remissions [31 and 46]. Therefore, we hypothesize that IL-15 will enhance T cell fitness in exhausted CD8+ T cells by restoring effector functions. We isolated peripheral blood mononuclear cells (PBMCs) from healthy and HNSCC donors as well as tumor infiltrating lymphocytes from our HNSCC donor. Cells were then cultured with or without IL-15 complexes for 48 hours. We found that IL-15 complexes increased proliferation and activation of early effector CD8+ T cells, the expression of immune checkpoint molecules, and effector molecules in our healthy and HNSCC donors. Additionally, IL-15 complexes enhanced the energetic profile of CD8+ T cells from our healthy donors. Thus, IL-15 complexes increased the normal responsive state of CD8+ T cells. |
