Journal article
Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition
- Abstract:
- High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP). Within The Cancer Genome Atlas (TCGA) EC cohort, significantly higher numbers of predicted neoantigens were demonstrated in POLE-mutant and MSI tumors compared to NSMP and p53-mutants. This was reflected by enhanced immune expression and infiltration in POLE-mutant and MSI tumors in both the TCGA cohort (mRNA expression) and the TransPORTEC cohort (immunohistochemistry) with high infiltration of CD8+ (90% and 69%), PD-1+ (73% and 69%) and PD-L1+ immune cells (100% and 71%). Notably, a subset of p53-mutant and NSMP cancers were characterized by signs of an antitumor immune response (43% and 31% of tumors with high infiltration of CD8+ cells, respectively), despite a low number of predicted neoantigens. In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich POLE-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1080/2162402X.2016.1264565
Authors
+ Oxford Cancer Centre, University of Oxford
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- Funding agency for:
- Church, D
- Grant:
- Clinician Scientist Award
+ Health Foundation
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- Funding agency for:
- Church, D
- Grant:
- Clinician Scientist Award
+ Academy of Medical Sciences
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- Funding agency for:
- Church, D
- Grant:
- Clinician Scientist Award
- Publisher:
- Taylor and Francis
- Journal:
- OncoImmunology More from this journal
- Volume:
- 6
- Issue:
- 2
- Pages:
- e1264565
- Publication date:
- 2016-11-01
- Acceptance date:
- 2016-11-17
- DOI:
- EISSN:
-
2162-4011
- ISSN:
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2162-402X
- Keywords:
- Pubs id:
-
pubs:660120
- UUID:
-
uuid:02765742-64ea-4d09-8b6b-9e513fe2eced
- Local pid:
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pubs:660120
- Source identifiers:
-
660120
- Deposit date:
-
2016-11-18
Terms of use
- Copyright holder:
- Church et al
- Copyright date:
- 2016
- Notes:
- Published with license by Taylor and Francis Group, LLC © Florine A. Eggink, Inge C. Van Gool, Alexandra Leary, Pamela M. Pollock, Emma J. Crosbie, Linda Mileshkin, Ekaterina S. Jordanova, JulienAdam, Luke Freeman-Mills, David N. Church, Carien L. Creutzberg, Marco De Bruyn, Hans W. Nijman, and Tjalling Bosse.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribu-tion, and reproduction in any medium, provided the original work is properly cited.
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