Adding the natural peptide LL-37 while growing immune cells called dendritic cells in the lab makes those cells better at waking up killer T‑cells that can attack tumors in mice. This effect is seen only for the CD8+ T‑cells, not the helper CD4+ ones, and it leads to tumor shrinkage in animal models.

Immunization of patients with autologous, <i>ex vivo</i> matured dendritic cell (DC) preparations, in order to prime antitumor T-cell responses, is the focus of intense research. Despite progress and approval of clinical approaches, significant enhancement of these personalized immunotherapies is urgently needed to improve efficacy. We show that immunotherapeutic murine and human DC, generated in the presence of the antimicrobial host defense peptide LL-37, have dramatically enhanced expansion and differentiation of cells with key features of the critical CD103⁺/CD141⁺ DC subsets, including enhanced cross-presentation and co-stimulatory capacity, and upregulation of CCR7 with improved migratory capacity. These LL-37-DC enhanced proliferation, activation and cytokine production by CD8⁺ (but not CD4⁺) T cells <i>in vitro</i> and <i>in vivo</i>. Critically, tumor antigen-presenting LL-37-DC increased migration of primed, activated CD8⁺ T cells into established squamous cell carcinomas in mice, and resulted in tumor regression. This advance therefore has the potential to dramatically enhance DC immunotherapy protocols.