Cancer-targeted photoimmunotherapy induces antitumor immunity and can be augmented by anti-PD-1 therapy for durable anticancer responses in an immunologically active murine tumor model.

The complex immunosuppressive nature of solid tumor microenvironments poses a significant challenge to generating efficacious and durable anticancer responses. Photoimmunotherapy is a cancer treatment strategy by which an antibody is conjugated with a non-toxic light-activatable dye. Following administration of the conjugate and binding to the target tumor, subsequent local laser illumination activates the dye, resulting in highly specific target cell membrane disruption. Here we demonstrate that photoimmunotherapy treatment elicited tumor necrosis, thus inducing immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs). Photoimmunotherapy-killed tumor cells activated dendritic cells (DC), leading to the production of proinflammatory cytokines, T cell stimulation, priming antigen-specific T cells, and durable memory T cell responses, which led complete responder mice to effectively reject new tumors upon rechallenge. PD-1 blockade in combination with photoimmunotherapy enhanced overall anticancer efficacy, including against anti-PD-1-resistant tumors. The combination treatment also elicited abscopal anticancer activity, as observed by reduction of distal, non-illuminated tumors, further demonstrating the ability of photoimmunotherapy to harness local and peripheral T cell responses. With this work we therefore delineate the immune mechanisms of action for photoimmunotherapy and demonstrate the potential for cancer-targeted photoimmunotherapy to be combined with other immunotherapy approaches for augmented, durable anticancer efficacy. Moreover, we demonstrate responses utilizing various immunocompetent mouse models, as well as in vitro data from human cells, suggesting broad translational potential.

Osteoporosis health beliefs of women with increased risk of the female athlete triad.

Women with increased risk of the female athlete triad (Triad) are more susceptible to osteoporosis compared to other women. The study included 65 women with increased risk of the Triad who had their osteoporosis health beliefs measured to assess their concern for the disease. Participants were female collegiate cross-country runners at different levels of competition, including National Association of Intercollegiate Athletics (NAIA) and National Collegiate Athletic Association (NCAA) Divisions III, II, and I. Although these participants have an increased risk of the Triad and are more susceptible to osteoporosis, on a scale of 1 to 5, results showed that they had low to moderate perceived susceptibility to osteoporosis with a mean score as high as 2.81 and moderate perceived severity of osteoporosis with a mean score as high as 3.38. A statistically significant difference in perceived susceptibility to osteoporosis was found between female collegiate cross-country runners in the NAIA and those in the NCAA DIII. Reasons that could explain relatively low levels of concern for osteoporosis in female collegiate cross-country runners and reasons for significant differences in perceived susceptibility to osteoporosis are given, and recommendations for health education and intervention to help care for this population are provided.