Single-Cell Multi-Tissue T Cell Clonal Dynamics Reveal Distinct Immune Coercion Landscapes in MSI and MSS Colorectal Cancer
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Le résumé fourni par la source
The efficacy of immunotherapy in colorectal cancer (CRC) has long been considered to be closely associated with microsatellite instability (MSI) status. Patients with microsatellite stable (MSS) tumors typically exhibit poor responses to PD-1/PD-L1 inhibitors and a poor prognosis, often being categorized as immunologically 'cold' tumors. However, some MSS patients can still achieve favorable therapeutic responses, sometimes even surpassing those of certain MSI patients. Immune-cold and immune-hot tumor phenotypes are largely determined by the abundance, clonal expansion, and functional states of tumor-infiltrating T cells. This suggests that immunotherapy responses are driven by dynamic remodeling of T-cell clonality rather than by MSI status alone. To elucidate the underlying T cell clonal dynamics, integrated single-cell transcriptome (scRNA-seq) and T cell receptor sequencing (scTCR-seq) data analyses from 43 blood and tissue samples of MSI and MSS colorectal cancer patients before and after anti-PD-1 therapy were performed. Using our developed TCR reconstruction pipeline (TORBiT), we systematically analyzed the clonal architecture of the TCR repertoire, inter-tissue migration, and its association with T-cell functional state transitions. From a TCR clonal kinetic perspective, we revealed two distinct modes of immune Coercion that may further affect the immune response: a "high-fluctuation, deep-exhaustion" pattern in MSI tumors and a "high-baseline, strong-suppression" pattern in MSS tumors. These findings provide a novel theoretical foundation and research perspective for understanding the responsiveness and resistance mechanisms to immune checkpoint inhibitors.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Single-Cell Multi-Tissue T Cell Clonal Dynamics Reveal Distinct Immune Coercion Landscapes in MSI and MSS Colorectal Cancer
- Date Crossref
- 16/03/2026
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Shanghai Ocean University pays non établi dans la noticeUniversité ou école supérieure
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Fudan University pays non établi dans la noticeUniversité ou école supérieure
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University of Shanghai for Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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College of Food Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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Shanghai-MOST Key Laboratory of Health and Disease Genomics pays non établi dans la noticeStructure de recherche
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School of Public Health pays non établi dans la noticeUniversité ou école supérieure
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School of Health Science and Engineering pays non établi dans la noticeUniversité ou école supérieure
Shanghai Ocean University, Fudan University et University of Shanghai for Science and Technology, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.