Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer

Dora Hammerl, John W. M. Martens, Mieke Timmermans, Marcel Smid, Anita M. Trapman-Jansen, Renée Foekens, Olga I. Isaeva, Leonie Voorwerk, Hayri E. Balcioglu, Rebecca Wijers, Iris Nederlof, Roberto Salgado, Hugo Horlings, Marleen Kok () and Reno Debets ()
Additional contact information
Dora Hammerl: Erasmus MC Cancer Institute
John W. M. Martens: Erasmus MC Cancer Institute
Mieke Timmermans: Erasmus MC Cancer Institute
Marcel Smid: Erasmus MC Cancer Institute
Anita M. Trapman-Jansen: Erasmus MC Cancer Institute
Renée Foekens: Erasmus MC Cancer Institute
Olga I. Isaeva: The Netherlands Cancer Institute
Leonie Voorwerk: The Netherlands Cancer Institute
Hayri E. Balcioglu: Erasmus MC Cancer Institute
Rebecca Wijers: Erasmus MC Cancer Institute
Iris Nederlof: The Netherlands Cancer Institute
Roberto Salgado: GZA-ZNA Ziekenhuizen
Hugo Horlings: The Netherlands Cancer Institute
Marleen Kok: The Netherlands Cancer Institute
Reno Debets: Erasmus MC Cancer Institute

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflamed phenotypes can be captured by a gene classifier that predicts prognosis of various cancers as well as anti-PD1 response of metastatic TNBC patients in a phase II trial. The excluded phenotype, which is associated with resistance to anti-PD1, demonstrates deposits of collagen-10, enhanced glycolysis, and activation of TGFβ/VEGF pathways; the ignored phenotype, also associated with resistance to anti-PD1, shows either high density of CD163+ myeloid cells or activation of WNT/PPARγ pathways; whereas the inflamed phenotype, which is associated with response to anti-PD1, revealed necrosis, high density of CLEC9A+ dendritic cells, high TCR clonality independent of neo-antigens, and enhanced expression of T cell co-inhibitory receptors.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25962-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25962-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25962-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().