dc.contributor.author | Khalique, S | |
dc.contributor.author | Nash, S | |
dc.contributor.author | Mansfield, D | |
dc.contributor.author | Wampfler, J | |
dc.contributor.author | Attygale, A | |
dc.contributor.author | Vroobel, K | |
dc.contributor.author | Kemp, H | |
dc.contributor.author | Buus, R | |
dc.contributor.author | Cottom, H | |
dc.contributor.author | Roxanis, I | |
dc.contributor.author | Jones, T | |
dc.contributor.author | von Loga, K | |
dc.contributor.author | Begum, D | |
dc.contributor.author | Guppy, N | |
dc.contributor.author | Ramagiri, P | |
dc.contributor.author | Fenwick, K | |
dc.contributor.author | Matthews, N | |
dc.contributor.author | Hubank, MJF | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Banerjee, S | |
dc.contributor.author | Natrajan, R | |
dc.date.accessioned | 2021-10-26T08:42:34Z | |
dc.date.available | 2021-10-26T08:42:34Z | |
dc.date.issued | 2021-07-30 | |
dc.identifier.citation | Cancers, 2021, 13 (15) | |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4842 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.doi | 10.3390/cancers13153854 | |
dc.description.abstract | Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with ARID1A purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date. Here, we characterised the immune landscape of OCCC by profiling a cohort of 33 microsatellite stable OCCCs at the genomic, gene expression and histological level using targeted sequencing, gene expression profiling using the NanoString targeted immune panel, and multiplex immunofluorescence to assess the spatial distribution and abundance of immune cell populations at the protein level. Analysis of these tumours and subsequent independent validation identified an immune-related gene expression signature associated with risk of recurrence of OCCC. Whilst histological quantification of tumour-infiltrating lymphocytes (TIL, Salgado scoring) showed no association with the risk of recurrence or ARID1A mutational status, the characterisation of TILs via multiplexed immunofluorescence identified spatial differences in immunosuppressive cell populations in OCCC. Tumour-associated macrophages (TAM) and regulatory T cells were excluded from the vicinity of tumour cells in low-risk patients, suggesting that high-risk patients have a more immunosuppressive microenvironment. We also found that TAMs and cytotoxic T cells were also excluded from the vicinity of tumour cells in ARID1A-mutated OCCCs compared to ARID1A wild-type tumours, suggesting that the exclusion of these immune effectors could determine the host response of ARID1A-mutant OCCCs to therapy. Overall, our study has provided new insights into the immune landscape and prognostic associations in OCCC and suggest that tailored immunotherapeutic approaches may be warranted for different subgroups of OCCC patients. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-07-27 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.3390/cancers13153854 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-07-30 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancers | |
pubs.issue | 15 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 13 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Gene Function | |
icr.researchteam | Translational Genomics | |
dc.contributor.icrauthor | Lord, Christopher | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Natrajan, Rachael | |