dc.contributor.author | Khaliq, AM | |
dc.contributor.author | Erdogan, C | |
dc.contributor.author | Kurt, Z | |
dc.contributor.author | Turgut, SS | |
dc.contributor.author | Grunvald, MW | |
dc.contributor.author | Rand, T | |
dc.contributor.author | Khare, S | |
dc.contributor.author | Borgia, JA | |
dc.contributor.author | Hayden, DM | |
dc.contributor.author | Pappas, SG | |
dc.contributor.author | Govekar, HR | |
dc.contributor.author | Kam, AE | |
dc.contributor.author | Reiser, J | |
dc.contributor.author | Turaga, K | |
dc.contributor.author | Radovich, M | |
dc.contributor.author | Zang, Y | |
dc.contributor.author | Qiu, Y | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | Fishel, ML | |
dc.contributor.author | Turk, A | |
dc.contributor.author | Gupta, V | |
dc.contributor.author | Al-Sabti, R | |
dc.contributor.author | Subramanian, J | |
dc.contributor.author | Kuzel, TM | |
dc.contributor.author | Sadanandam, A | |
dc.contributor.author | Waldron, L | |
dc.contributor.author | Hussain, A | |
dc.contributor.author | Saleem, M | |
dc.contributor.author | El-Rayes, B | |
dc.contributor.author | Salahudeen, AA | |
dc.contributor.author | Masood, A | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-07-19T10:21:57Z | |
dc.date.available | 2022-07-19T10:21:57Z | |
dc.date.issued | 2022-05-11 | |
dc.identifier | ARTN 113 | |
dc.identifier | 10.1186/s13059-022-02677-z | |
dc.identifier.citation | Genome Biology, 2022, 23 (1), pp. 113 - | |
dc.identifier.issn | 1474-7596 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5243 | |
dc.identifier.eissn | 1474-760X | |
dc.identifier.eissn | 1474-760X | |
dc.identifier.doi | 10.1186/s13059-022-02677-z | |
dc.description.abstract | BACKGROUND: Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. RESULTS: Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. CONCLUSIONS: Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients. | |
dc.format | Electronic | |
dc.format.extent | 113 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.relation.ispartof | Genome Biology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | CMS classification | |
dc.subject | Cancer-associated fibroblast | |
dc.subject | Colorectal cancer | |
dc.subject | Immunotherapy | |
dc.subject | Single-cell analysis | |
dc.subject | Stromal signatures | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Complement C1q | |
dc.subject | Humans | |
dc.subject | Microsatellite Instability | |
dc.subject | Transcriptome | |
dc.subject | Tumor Microenvironment | |
dc.title | Refining colorectal cancer classification and clinical stratification through a single-cell atlas. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-04-21 | |
dc.date.updated | 2022-07-19T10:21:27Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1186/s13059-022-02677-z | |
rioxxterms.licenseref.startdate | 2022-05-11 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35538548 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published online | |
pubs.volume | 23 | |
icr.researchteam | Systems - Precision Med | |
dc.contributor.icrauthor | Sadanandam, Anguraj | |
icr.provenance | Deposited by Mr Arek Surman on 2022-07-19. Deposit type is initial. No. of files: 1. Files: Refining colorectal cancer classification and clinical stratification through a single-cell atlas.pdf | |