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dc.contributor.authorGoff, PH
dc.contributor.authorRiolobos, L
dc.contributor.authorLaFleur, BJ
dc.contributor.authorSpraker, MB
dc.contributor.authorSeo, YD
dc.contributor.authorSmythe, KS
dc.contributor.authorCampbell, JS
dc.contributor.authorPierce, RH
dc.contributor.authorZhang, Y
dc.contributor.authorHe, Q
dc.contributor.authorKim, EY
dc.contributor.authorSchaub, SK
dc.contributor.authorKane, GM
dc.contributor.authorMantilla, JG
dc.contributor.authorChen, EY
dc.contributor.authorRicciotti, R
dc.contributor.authorThompson, MJ
dc.contributor.authorCranmer, LD
dc.contributor.authorWagner, MJ
dc.contributor.authorLoggers, ET
dc.contributor.authorJones, RL
dc.contributor.authorMurphy, E
dc.contributor.authorBlumenschein, WM
dc.contributor.authorMcClanahan, TK
dc.contributor.authorEarls, J
dc.contributor.authorFlanagan, KC
dc.contributor.authorLaFranzo, NA
dc.contributor.authorKim, TS
dc.contributor.authorPollack, SM
dc.date.accessioned2022-04-27T09:17:30Z
dc.date.available2022-04-27T09:17:30Z
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2022, 28 (8), pp. 1701 - 1711en
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5098
dc.identifier.eissn1557-3265en_US
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-21-4239en_US
dc.identifier.doi10.1158/1078-0432.ccr-21-4239
dc.description.abstract<h4>Purpose</h4>To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design.<h4>Experimental design</h4>Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis.<h4>Results</h4>All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy. The most prevalent immune cells in the tumor before neoadjuvant therapy were myeloid cells (45% of all immune cells) and B cells (37%), with T (13%) and natural killer (NK) cells (5%) also present. Neoadjuvant therapy significantly increased the total immune cells infiltrating the tumors across all histologic subtypes for patients receiving neoadjuvant radiotherapy with or without chemotherapy. An increase in the percentage of monocytes and macrophages, particularly M2 macrophages, B cells, and CD4+ T cells was observed postneoadjuvant therapy. Upregulation of genes and cytokines associated with antigen presentation was also observed, and a favorable pathologic response (≥90% necrosis postneoadjuvant therapy) was associated with an increase in monocytic infiltrate. Upregulation of the T-cell checkpoint TIM3 and downregulation of OX40 were observed posttreatment.<h4>Conclusions</h4>Standard neoadjuvant therapy induces both immunostimulatory and immunosuppressive effects within a complex sarcoma microenvironment dominated by myeloid and B cells. This work informs ongoing efforts to incorporate immune checkpoint inhibitors and novel immunotherapies into the neoadjuvant setting for STSs.en
dc.formatPrinten_US
dc.format.extent1701 - 1711en_US
dc.languageengen_US
dc.language.isoengen
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden
dc.subjectHumansen
dc.subjectSarcomaen
dc.subjectSoft Tissue Neoplasmsen
dc.subjectPrognosisen
dc.subjectNeoadjuvant Therapyen
dc.subjectRetrospective Studiesen
dc.subjectImmunityen
dc.subjectTumor Microenvironmenten
dc.titleNeoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.en
dc.typeJournal Article
dcterms.dateAccepted2022-02-01
rioxxterms.versionAMen
rioxxterms.versionofrecord10.1158/1078-0432.ccr-21-4239en
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Researchen_US
pubs.issue8en_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.volume28en_US
pubs.embargo.termsNot knownen_US
icr.researchteamSarcoma Clinical Trials (R Jones)
dc.contributor.icrauthorJones, Robin


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