A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Cross-presentation of antigens from dead tumor cells by type 1 conventional dendritic cells (cDC1s) is thought to underlie priming of anti-cancer CD8⁺ T cells. cDC1 express high levels of DNGR-1 (a.k.a. CLEC9A), a receptor that binds to F-actin exposed by dead cell debris and promotes cross-presentation of associated antigens. Here, we show that secreted gelsolin (sGSN), an extracellular protein, decreases DNGR-1 binding to F-actin and cross-presentation of dead cell-associated antigens by cDC1s. Mice deficient in sGsn display increased DNGR-1-dependent resistance to transplantable tumors, especially ones expressing neoantigens associated with the actin cytoskeleton, and exhibit greater responsiveness to cancer immunotherapy. In human cancers, lower levels of intratumoral sGSN transcripts, as well as presence of mutations in proteins associated with the actin cytoskeleton, are associated with signatures of anti-cancer immunity and increased patient survival. Our results reveal a natural barrier to cross-presentation of cancer antigens that dampens anti-tumor CD8⁺ T cell responses.

Burnout in health care professionals (HCPs) results from exposure to psychosocial risks at work. Left unaddressed, burnout can lead to chronic health problems, increased staff turnover, reduced work hours, absenteeism, and early retirement from clinical practice, thus impacting patient care. The European Society for Medical Oncology (ESMO) Resilience Task Force (RTF) was established in December 2019 to support the well-being of oncology HCPs globally. This ESMO RTF position paper aims to provide a set of recommendations to optimise well-being and mitigate burnout in oncology, and to help individuals and institutions maintain the delivery of optimal cancer care. Recommendations were developed by a diverse multinational panel of interprofessional experts based on the key findings from three previously reported ESMO RTF surveys. Several recurrent work-related psychosocial risks in oncology were identified; in particular, concerns about workload and professional development. The need for flexible work patterns, continued use of virtual resources, well-being resources, and targeted support for at-risk groups were highlighted as key considerations to safeguard HCPs' health and prevent burnout. In total, 11 recommendations relating to three priority themes were developed: (i) information and training; (ii) resources; (iii) activism and advocacy. Optimising the well-being of oncology HCPs is essential for the provision of high-quality, sustainable care for patients globally. The ESMO RTF will continue its mission and is rolling out several initiatives and activities to support the implementation of these recommendations.