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*, Reno Debets*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
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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.

Original languageEnglish
Article number5668
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 27 Sep 2021

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