Show simple item record

dc.contributor.authorGazinska, P
dc.contributor.authorMilton, C
dc.contributor.authorIacovacci, J
dc.contributor.authorWard, J
dc.contributor.authorBuus, R
dc.contributor.authorAlaguthurai, T
dc.contributor.authorGraham, R
dc.contributor.authorAkarca, A
dc.contributor.authorLips, E
dc.contributor.authorNaidoo, K
dc.contributor.authorWesseling, J
dc.contributor.authorMarafioti, T
dc.contributor.authorCheang, M
dc.contributor.authorGillett, C
dc.contributor.authorWu, Y
dc.contributor.authorKhan, A
dc.contributor.authorMelcher, A
dc.contributor.authorSalgado, R
dc.contributor.authorDowsett, M
dc.contributor.authorTutt, A
dc.contributor.authorRoxanis, I
dc.contributor.authorHaider, S
dc.contributor.authorIrshad, S
dc.date.accessioned2022-09-28T13:16:20Z
dc.date.available2022-09-28T13:16:20Z
dc.date.issued2022-09-26
dc.identifier.citationClinical Cancer Research, 2022, pp. OF1 - OF15en_US
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5511
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-22-0543
dc.identifier.doi10.1158/1078-0432.ccr-22-0543
dc.description.abstract<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)–resistant triple-negative breast cancer (TNBC) and ER+HER2– breast cancer disease.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2–n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2– cases. Bright-field hematoxylin and eosin assessment allowed for tumor-infiltrating lymphocyte (TIL) evaluation in all cases. Multiplexed immunofluorescence was used to identify the abundance and distribution of immune cell subsets. Levels of checkpoints including PD-1/PD-L1 expression were also quantified. Findings were then validated using expression profiling of cancer and immune-related genes. Cytometry by time-of-flight characterized the dynamic changes in circulating immune cells with NAC.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>RCB II/III TNBC and ER+HER2– breast cancer were immunologically “cold” at baseline and end of NAC. Although the distribution of immune cell subsets across subtypes was similar, the mRNA expression profiles were both subtype- and chemotherapy-specific. TNBC RCB II/III disease was enriched with genes related to neutrophil degranulation, and displayed strong interplay across immune and cancer pathways. We observed similarities in the dynamic changes in B-cell biology following NAC irrespective of subtype. However, NAC induced changes in the local and circulating tumor immune microenvironment (TIME) that varied by subtype and response. Specifically, in TNBC residual disease, we observed downregulation of stimulatory (CD40/OX40L) and inhibitory (PD-L1/PD-1) receptor expression and an increase in NK cell populations (especially non-cytolytic, exhausted CD56dimCD16–) within both the local TIME and peripheral white cell populations.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>This study identifies several potential immunologic pathways in residual disease, which may be targeted to benefit high-risk patients.</jats:p> </jats:sec>
dc.format.extentOF1 - OF15
dc.languageen
dc.language.isoengen_US
dc.publisherAmerican Association for Cancer Research (AACR)en_US
dc.relation.ispartofClinical Cancer Research
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleDynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancersen_US
dc.typeJournal Article
dcterms.dateAccepted2022-08-12
dc.date.updated2022-09-28T10:32:40Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1158/1078-0432.ccr-22-0543en_US
rioxxterms.licenseref.startdate2022-09-26
rioxxterms.typeJournal Article/Reviewen_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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Locoregional Therapy Team
pubs.publication-statusPublished online
pubs.publisher-urlhttp://dx.doi.org/10.1158/1078-0432.ccr-22-0543
icr.provenanceDeposited by Dr Aadil Khan on 2022-09-28. Deposit type is initial. No. of files: 1. Files: ccr-22-0543.pdf


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc-nd/4.0/
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/