Carlson, P. M. | bioRxiv Science

bioRxiv2025

Immune-mediated Engagement of T Regulatory Cells with Tumor Cells Results in Trogocytosis and Tumor Cell Killing.

Despite advances in treatment, >50% of patients with advanced melanoma are unresponsive to current therapies. Using the B78-D14 melanoma model (GD2+/MHC-I-/MHC-II+), we can cure mice with a regimen that includes radiation therapy (RT) in combination with immunocytokine (IC; anti-GD2 monoclonal antibody linked to IL-2) while establishing immunological memory. We interrogated the role of T cells in the antitumor and memory responses following RT+IC. We show a requirement for CD4, but not CD8 T cells, to achieve both the initial and memory responses. Upon IC-induced cell-cell contact, subsets of CD4 T cells, including Foxp3 T regulatory cells, trogocytose GD2 from tumor cells, acquire cytotoxic granules, and kill tumor cells. These results were confirmed using human tumor cell lines. These findings reveal that CD4 T regulatory cells, upon immunologically-induced binding to tumor cells, can trogocytose tumor antigens and directly kill tumor cells, redefining their potential role in antitumor immunity.

cancer biology↗

bioRxiv2024

Understanding organism-habitat relationships and critically evaluating reference areas is key to marine protected area assessment

Marine Protected Areas (MPAs) have been implemented globally as a conservation tool to improve the health and function of marine ecosystems. Research has focused on assessing MPA effectiveness, however certain habitats and communities are often avoided because they are difficult or expensive to monitor. Mesophotic (30-100m) rocky reef fish communities are a valuable commercial and recreational resource that is highly targeted but often overlooked in monitoring due to depth restricted sampling. We used two MPAs in Californias statewide protection network, along with parried reference sites, to test how protection status along with environmental conditions influenced the abundance and biomass of three highly targeted species with varying life histories and habitat preferences. Depth and habitat were strong predictors for all groups; ocean whitefish (Caulolatilus princeps), California sheephead (Semicossyphus pulcher), and targeted rockfish (Sebastes spp). The pattern of these effects however, differed between the species groups and the influence of protection was mixed. This work highlights how species with high habitat affinities benefit differently from protection, as a function of depth and habitat representation within the MPA/reference pair. To accurately evaluate MPAs, and the network as a whole, researchers must recognize organism-habitat relationships and incorporate them when assessing conservation efforts.

ecology↗