Publications by authors named "Grace E Crossland"
Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes ("lymphonets") emerged as a distinctive feature of the anti-cancer immune response.
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- CD8 T cell responses to different tumor neoantigens happen at the same time, but how they influence each other and overall tumor control is not well understood.
- In a mouse model of lung adenocarcinoma, it was discovered that the most stable binding of an antigen to MHC drives the dominant CD8 T cell expansion, while subdominant T cells show a TCF1 progenitor phenotype linked to immune checkpoint blockade (ICB) therapy responses.
- However, a dysfunctional subset of subdominant TCF1 cells, identified by markers like CCR6 and Tc17 differentiation, limits their benefit from ICB, but using vaccination helps eliminate these cells and enhances the subdominant T cell response against tumors.