Sade-Feldman et al from the Massachusetts General Hospital Cancer Center, the Broad Institute, the Dana Farber Cancer Institute and others demonstrated in the Cell paper that:
- Single-cell RNA-seq reveals distinct CD45 + cells associated with clinical outcome
- The balance between two CD8 + T cell states is linked with tumor regression
- TCF7 +CD8 + T cell frequency in tumor tissue predicts response and better survival
- Dual blockade of CD39 with different checkpoint proteins enhances immunity
Ex vivo culture of murine-derived organotypic tumor spheroids (MDOTS) in AIM Biotech chips is able to recapitulate the immune checkpoint response. These assays were used to validate the authors' discoveries by co-culturing the MDOTS with defined CD8+ T cell populations (CD39+/TIM3+, CD39-/TIM3- or mixed 1:1) (see figure).