Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade.

BACKGROUND: Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing. METHODS: ID8 tumor cells were injected intraperitoneally into mice. Mice were treated with Th17-DC or conventional DC (cDC) vaccine alone or with immune checkpoint blockade (ICB). Systemic immunity, tumor associated immunity, tumor size and survival were examined using a variety of experimental strategies. RESULTS: Th17-DC vaccines increased Th17 T cells in the tumor microenvironment, reshaped the myeloid microenvironment, and improved mouse survival compared with cDC vaccines. ICB had limited efficacy in OC, but Th17-inducing DC vaccination sensitized it to anti-PD-1 ICB, resulting in durable progression-free survival by overcoming IL-10-mediated resistance. Th17-DC vaccine efficacy, alone or with ICB, was mediated by CD4 T cells, but not CD8 T cells. CONCLUSIONS: These findings emphasize using biologically relevant immune modifiers, like Th17-DC vaccines, in OC treatment to reshape the tumor microenvironment and enhance clinical responses to ICB therapy.

Building Patient-Physician Trust: A Medical Student Perspective.

Public trust in physicians has declined over the last 50 years. Future physicians will need to mend the patient-physician trust relationship. In conjunction with the American Medical Association's Accelerating Change in Medical Education initiative, the Mayo Clinic Alix School of Medicine implemented the Science of Health Care Delivery (SHCD) curriculum-a 4-year curriculum that emphasizes interdisciplinary training across population-centered care; person-centered care; team-based care; high-value care; leadership; and health policy, economics, and technology-in 2015. In this medical student perspective, the authors highlight how the SHCD curriculum has the potential to address issues that have eroded patient-physician trust. The curriculum reaches this aim through didactic and/or experiential teachings in health equity, cultural humility and competence, shared decision making, patient advocacy, and safety and quality of care. It is the authors' hope that novel medical education programs such as the SHCD curriculum will allow the nation's future physicians to own their role in rebuilding and fostering public trust in physicians and the health care system.