Heaton, A. | Search bioRxiv

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↗

bioRxiv2021

Hybridization and Low Genetic Diversity in the Endangered Alabama Red-Bellied Turtle (Pseudemys alabamensis)

Pseudemys alabamensis is one of the most endangered turtle species in the United States due to its small population size and restricted geographic distribution in coastal Alabama and Mississippi. Increased urbanization and climate change impacts in the region further threaten this species. Populations of P. alabamensis are geographically isolated from one another by land and salt water, which could act as barriers to intraspecific gene flow. It is currently unknown how differentiated these isolated populations are from one another or whether they have experienced reductions in population size. Previous work found morphological differences between Alabama and Mississippi populations, suggesting that they may be evolutionarily distinct. Other Pseudemys turtles such as P. concinna and P. floridana occur within the same geographic area as P. alabamensis and are known to hybridize with each other. These more abundant species could further threaten the unique genetic identity of P. alabamensis through introgression. In order to evaluate the endangered status of P. alabamensis and the level of hybridization with other species, we used the mitochondrial (mtDNA) control region and nuclear microsatellite markers to assess genetic variation within and among populations of this species throughout its range and estimate admixture with co-occurring Pseudemys species. Genetic diversity of P. alabamensis was lower than expected at both markers (no variation in mtDNA and excess of homozygosity in microsatellites). We found evidence of genetic differentiation between Alabama and Mississippi populations as well as two populations (Fowl River, Alabama and Biloxi, Mississippi) with low estimated breeding sizes and signs of inbreeding. Finally, we found evidence of admixture of P. alabamensis with P. concinna/P. floridana and Pseudemys peninsularis (a species not native to Alabama or Mississippi). Our results indicate that P. alabamensis is highly endangered throughout its range and threatened by both low population sizes and hybridization. In order to improve the species chances of survival, focus should be placed on habitat preservation, maintenance of genetic diversity within both Mississippi and Alabama populations, and regular population monitoring activities such as nest surveillance and estimates of recruitment.

evolutionary biology↗