Bibliographic Details
| Title: |
Single cell dynamics of tumor specificity vs bystander activity in CD8+ T cells define the diverse immune landscapes in colorectal cancer |
| Authors: |
Daniel Morales Borràs, Sara Verbandt, Markus Ausserhofer, Gregor Sturm, Jinyeong Lim, Gil Arasa Verge, Isaure Vanmeerbeek, Raquel S. Laureano, Jannes Govaerts, Jenny Sprooten, Yourae Hong, Rebecca Wall, Gert De Hertogh, Xavier Sagaert, Gabriele Bislenghi, André D’Hoore, Albert Wolthuis, Francesca Finotello, Woong-Yang Park, Stefan Naulaerts, Sabine Tejpar, Abhishek D. Garg |
| Source: |
Cell Discovery, Vol 9, Iss 1, Pp 1-30 (2023) |
| Publisher Information: |
Nature Publishing Group, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract CD8+ T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against microsatellite stable (MSS) CRC is limited. Little is known about the most critical features of CRC CD8+ T cells that together determine the diverse immune landscapes and contrasting ICB responses. Hence, we pursued a deep single cell mapping of CRC CD8+ T cells on transcriptomic and T cell receptor (TCR) repertoire levels in a diverse patient cohort, with additional surface proteome validation. This revealed that CRC CD8+ T cell dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) TCR antigen-specificities, and environmental cues like gut microbiome or colon tissue-specific ‘self-like’ features. MSI CRC CD8+ T cells showed tumor-specific activation reminiscent of canonical ‘T cell hot’ tumors, whereas the MSS CRC CD8+ T cells exhibited tumor unspecific or bystander-like features. This was accompanied by inflammation reminiscent of ‘pseudo-T cell hot’ tumors. Consequently, MSI and MSS CRC CD8+ T cells showed overlapping phenotypic features that differed dramatically in their TCR antigen-specificities. Given their high discriminating potential for CD8+ T cell features/specificities, we used the single cell tumor-reactive signaling modules in CD8+ T cells to build a bulk tumor transcriptome classification for CRC patients. This “Immune Subtype Classification” (ISC) successfully distinguished various tumoral immune landscapes that showed prognostic value and predicted immunotherapy responses in CRC patients. Thus, we deliver a unique map of CRC CD8+ T cells that drives a novel tumor immune landscape classification, with relevance for immunotherapy decision-making. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2056-5968 |
| Relation: |
https://doaj.org/toc/2056-5968 |
| DOI: |
10.1038/s41421-023-00605-4 |
| Access URL: |
https://doaj.org/article/b6bbbd98e72c4ea192406d7073bc5f95 |
| Accession Number: |
edsdoj.b6bbbd98e72c4ea192406d7073bc5f95 |
| Database: |
Directory of Open Access Journals |
