Our latest work on deep single cell mapping of CD8+T cell in colorectal cancer patients leading to first Artificial Intelligence classification for Immunotherapy – Cell Stress and Immunity Lab

Cell Stress and Immunity Lab shared on their X/Twitter page:

”Thrilled to share our latest work on deep single cell mapping of CD8+T cell in colorectal cancer patients leading to first Artificial Intelligence classification for Immunotherapy! Thanks Sabine Tejpar!

We did single cell mapping of CD8+T cells on transcriptomic (scRNAseq) and T cell receptor (scTCRseq) levels in a diverse patient cohort, and saw that subpopulation phenotypes of CD8+T cells overlapped substantially in MSI and MSS CRC. Read more here. 

Remarkably, MSI vs. MSS CRC showed contrasting tumor-reactive signaling within IFNG+CD8+T cells, highly distinct T cell signaling hubs and contrasting TCR vs bystander activation. Also MSS CRC highly enriched IL17A-HI MAITs MAIT cells. Read more here.

TCR repertoire of IFNG+CD8+T cells in MSS CRC had low diversity and viral specificity. MSI CRC CD8+T cells with exclusive (possibly neoantigenic) TCRs had immunogenic features and TOX-HI memory-exhaustion, which contrasted with MSS CRC. Read more here.

Importantly, the CD8+T cell features exhibited contrasting multi-layered clustering in MSI vs MSS CRC patients. Such an overarching multi-variable and multi-dimensional view of CRC CD8+T cell immunology has never been shown before! Read more here.

Curiously, CD8+T cell dynamics operated as patient-dependent CRC strata. Despite a sizable patient-to-patient variation, MSI patients bifurcated into more homogeneous clusters, but MSS patients exhibited very heterogeneous clusters! Read more here.

Innovatively CD8T single cell features stratified colorectal cancer patients into new immune-subtype classification (ISC) system. ISC worked as Artificial Intelligence framework for prognostic impact and predicted Immunotherapy benefit! Read here.

Conclusion: MSI CRC CD8+T cell show tumor-specific activation reminiscent of canonical ‘T cell hot’ tumors, but MSS CRC CD8+T cell show tumor unspecific/bystander features, along with inflammation reminiscent of ‘pseudo-T cell hot’ tumors! Read here.

Thanks to all collaborators (esp. our CSI team) for making this brilliant work possible, including brilliant Sabine Tejpar lab. Stefan Naulaerts, Sara Verbandt, Francesca Finotello team! Thanks to our funders: KU Leuven, FWO, VLIR-UOS, UZ Leuven! ”

For the article click here.
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Source: Cell Stress and Immunity Lab/Twitter