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dc.contributor.authorSchroeder, BA
dc.contributor.authorZhang, Y
dc.contributor.authorSmythe, KS
dc.contributor.authorDesai, P
dc.contributor.authorThomas, A
dc.contributor.authorViveiros, P
dc.contributor.authorAlexiev, BA
dc.contributor.authorObeidin, F
dc.contributor.authorChen, EY
dc.contributor.authorCranmer, LD
dc.contributor.authorWagner, MJ
dc.contributor.authorJones, RL
dc.contributor.authorCampbell, JS
dc.contributor.authorPierce, RH
dc.contributor.authorHe, Q
dc.contributor.authorPollack, SM
dc.date.accessioned2022-05-25T13:25:14Z
dc.date.available2022-05-25T13:25:14Z
dc.date.issued2022-03-02
dc.identifier.citationCancers, 2022, 14 (5), pp. 1290 - ?en
dc.identifier.issn2072-6694
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5148
dc.identifier.eissn2072-6694en_US
dc.identifier.eissn2072-6694
dc.identifier.doi10.3390/cancers14051290en_US
dc.identifier.doi10.3390/cancers14051290
dc.description.abstractPatients with metastatic soft tissue sarcoma (STS) have a poor prognosis and few available systemic treatment options. Trabectedin is currently being investigated as a potential adjunct to immunotherapy as it has been previously shown to kill tumor-associated macrophages. In this retrospective study, we sought to identify biomarkers that would be relevant to trials combining trabectedin with immunotherapy. We performed a single-center retrospective study of sarcoma patients treated with trabectedin with long-term follow-up. Multiplex gene expression analysis using the NanoString platform was assessed, and an exploratory analysis using the lasso-penalized Cox regression and kernel association test for survival (MiRKAT-S) methods investigated tumor-associated immune cells and correlated their gene signatures to patient survival. In total, 147 sarcoma patients treated with trabectedin were analyzed, with a mean follow-up time of 5 years. Patients with fewer prior chemotherapy regimens were more likely to stay on trabectedin longer (pairwise correlation = -0.17, p = 0.04). At 5 years, increased PD-L1 expression corresponded to worse outcomes (HR = 1.87, p = 0.04, q = 0.199). Additionally, six immunologic gene signatures were associated with up to 7-year survival by MiRKAT-S, notably myeloid-derived suppressor cells (p = 0.023, q = 0.058) and M2 macrophages (p = 0.03, q = 0.058). We found that the number of chemotherapy regimens prior to trabectedin negatively correlated with the number of trabectedin cycles received, suggesting that patients may benefit from receiving trabectedin earlier in their therapy course. The correlation of trabectedin outcomes with immune cell infiltrates supports the hypothesis that trabectedin may function as an immune modulator and supports ongoing efforts to study trabectedin in combination with immunotherapy. Furthermore, tumors with an immunosuppressive microenvironment characterized by macrophage infiltration and high PD-L1 expression were less likely to benefit from trabectedin, which could guide clinicians in future treatment decisions.en_US
dc.formatElectronicen_US
dc.format.extent1290 - ?en_US
dc.languageengen_US
dc.language.isoengen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleImmunologic Gene Signature Analysis Correlates Myeloid Cells and M2 Macrophages with Time to Trabectedin Failure in Sarcoma Patients.en
dc.typeJournal Article
dcterms.dateAccepted2022-02-26
rioxxterms.versionVoRen
rioxxterms.versionofrecord10.3390/cancers14051290en
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en
rioxxterms.licenseref.startdate2022-03-02
dc.relation.isPartOfCancersen_US
pubs.issue5en_US
pubs.notesNot knownen_US
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume14en_US
pubs.embargo.termsNot knownen_US
icr.researchteamSarcoma Clinical Trials (R Jones)
dc.contributor.icrauthorJones, Robinen_US


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