Journal Article

DKFZ-2026-00398

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Temporal and spatial composition of the tumor microenvironment predicts response to immune checkpoint inhibition in metastatic TNBC.

Greenwald, N. F. ; Nederlof, I. ; Sowers, C. ; Ding, D. Y. ; Park, S. ; Kong, A. ; Houlahan, K. E. ; Varra, S. R. ; de Graaf, M. ; Geurts, V. ; Liu, C. C. ; Ranek, J. S. ; Voorwerk, L. ; de Maaker, M. ; Kagel, A. ; McCaffrey, E. ; Khan, A. ; Yeh, C. Y. ; Fullaway, C. C. ; Khair, Z. ; Simon, B. G. ; Bai, Y. ; Piyadasa, H. ; Risom, T. ; Delmastro, A. ; Hartmann, F.DKFZ* ; Mangiante, L. ; Sotomayor-Vivas, C. ; Bendall, S. C. ; Schumacher, T. N. ; Ma, Z. ; Bosse, M. ; van de Vijver, M. J. ; Tibshirani, R. ; Horlings, H. M. ; Curtis, C. ; Kok, M. ; Angelo, M.

2026
Nature Research London

Abstract: Immune checkpoint inhibition (ICI) benefits only a subset of patients with metastatic triple-negative breast cancer and determinants of response remain unclear. We assembled a longitudinal cohort of 103 female patients from the phase 2 TONIC trial, with samples spanning primary tumors, pretreatment metastases and on-treatment metastases during nivolumab therapy. We profiled 37 proteins in 270 tumors using highly multiplexed imaging and developed SpaceCat, an open-source pipeline that extracts more than 800 imaging features per sample, including cell density, diversity, spatial interactions and functional marker expression. Metastatic but not primary tumors contained features predictive of outcome. Spatial metrics such as immune diversity and T cell infiltration at tumor borders were most informative, while ratios of T cells to cancer cells and PDL1 on myeloid cells were also associated with response. Multivariate models stratified patients with the highest performance on treatment (area under the curve = 0.90). Bulk RNA-seq confirmed the predictive value of on-treatment samples. These findings highlight the value of longitudinal profiling to resolve evolving tumor microenvironment dynamics driving ICI response.

Note: epub

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Contributing Institute(s):

1. NWG Systemimmunologie und Einzelzell-Biologie (D260)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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