Author
Listed:
- Xiao Qian Wang
(University of Cambridge)
- Esther Danenberg
(University of Cambridge)
- Chiun-Sheng Huang
(National Taiwan University Hospital, College of Medicine, National Taiwan University and Taiwan Breast Cancer Consortium)
- Daniel Egle
(Medical University Innsbruck)
- Maurizio Callari
(Fondazione Michelangelo)
- Begoña Bermejo
(Hospital Clínico Universitario de Valencia, Biomedical Research Institute INCLIVA
Universidad de Valencia
Oncology Biomedical Research National Network (CIBERONC-ISCIII))
- Matteo Dugo
(San Raffaele Hospital)
- Claudio Zamagni
(IRCCS Azienda Ospedaliero-universitaria di Bologna)
- Marc Thill
(Agaplesion Markus Krankenhaus)
- Anton Anton
(Hospital Universitario Miguel Servet)
- Stefania Zambelli
(San Raffaele Hospital)
- Stefania Russo
(Azienda Sanitaria Universitaria Friuli Centrale)
- Eva Maria Ciruelos
(Hospital Universitario 12 de Octubre)
- Richard Greil
(Paracelsus Medical University Salzburg
Salzburg Cancer Research Institute-CCCIT
Cancer Cluster Salzburg)
- Balázs Győrffy
(Semmelweis University
Institute of Enzymology)
- Vladimir Semiglazov
(NN Petrov Research Institute of Oncology)
- Marco Colleoni
(IRCCS)
- Catherine M. Kelly
(Dublin and Cancer Trials Ireland Breast Group)
- Gabriella Mariani
(Fondazione IRCSS - Istituto Nazionale Tumori)
- Lucia Mastro
(UO Clinica di Oncologia Medica
Dipartimento di Medicina Interna e Specialità Mediche (Di.M.I.), Università di Genova)
- Olivia Biasi
(IRCCS)
- Robert S. Seitz
(Oncocyte Corporation)
- Pinuccia Valagussa
(Fondazione Michelangelo)
- Giuseppe Viale
(IRCCS
University of Milan)
- Luca Gianni
(Fondazione Michelangelo)
- Giampaolo Bianchini
(Fondazione Michelangelo
San Raffaele Hospital)
- H. Raza Ali
(University of Cambridge
Addenbrookes Hospital)
Abstract
Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.
Suggested Citation
Xiao Qian Wang & Esther Danenberg & Chiun-Sheng Huang & Daniel Egle & Maurizio Callari & Begoña Bermejo & Matteo Dugo & Claudio Zamagni & Marc Thill & Anton Anton & Stefania Zambelli & Stefania Russo , 2023.
"Spatial predictors of immunotherapy response in triple-negative breast cancer,"
Nature, Nature, vol. 621(7980), pages 868-876, September.
Handle:
RePEc:nat:nature:v:621:y:2023:i:7980:d:10.1038_s41586-023-06498-3
DOI: 10.1038/s41586-023-06498-3
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Cited by:
- Lenka Kasikova & Jana Rakova & Michal Hensler & Tereza Lanickova & Jana Tomankova & Josef Pasulka & Jana Drozenova & Katerina Mojzisova & Anna Fialova & Sarka Vosahlikova & Jan Laco & Ales Ryska & Pav, 2024.
"Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer,"
Nature Communications, Nature, vol. 15(1), pages 1-19, December.
- Kenro Tanoue & Hirofumi Ohmura & Koki Uehara & Mamoru Ito & Kyoko Yamaguchi & Kenji Tsuchihashi & Yudai Shinohara & Peng Lu & Shingo Tamura & Hozumi Shimokawa & Taichi Isobe & Hiroshi Ariyama & Yoshih, 2024.
"Spatial dynamics of CD39+CD8+ exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer,"
Nature Communications, Nature, vol. 15(1), pages 1-18, December.
- Weiyue Zheng & Wanda Marini & Kiichi Murakami & Valentin Sotov & Marcus Butler & Chiara Gorrini & Pamela S. Ohashi & Michael Reedijk, 2024.
"Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy,"
Nature Communications, Nature, vol. 15(1), pages 1-13, December.
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