In situ tumour arrays reveal early environmental control of cancer immunity

Guadalupe Ortiz-Muñoz, Markus Brown, Catherine B. Carbone, Ximo Pechuan-Jorge, Vincent Rouilly, Henrik Lindberg, Alex T. Ritter, Gautham Raghupathi, Qianbo Sun, Tess Nicotra, Shreya R. Mantri, Angela Yang, Jonas Doerr, Deepti Nagarkar, Spyros Darmanis, Benjamin Haley, Sanjeev Mariathasan, Yulei Wang, Carlos Gomez-Roca, Carlos Eduardo Andrea, David Spigel, Thomas Wu, Lelia Delamarre, Johannes Schöneberg, Zora Modrusan, Richard Price, Shannon J. Turley, Ira Mellman and Christine Moussion ()
Additional contact information
Guadalupe Ortiz-Muñoz: Genentech
Markus Brown: Genentech
Catherine B. Carbone: Genentech
Ximo Pechuan-Jorge: Genentech
Vincent Rouilly: Genentech
Henrik Lindberg: Genentech
Alex T. Ritter: Genentech
Gautham Raghupathi: Stanford University
Qianbo Sun: Genentech
Tess Nicotra: Genentech
Shreya R. Mantri: Genentech
Angela Yang: Genentech
Jonas Doerr: Genentech
Deepti Nagarkar: Genentech
Spyros Darmanis: Genentech
Benjamin Haley: Genentech
Sanjeev Mariathasan: Genentech
Yulei Wang: Genentech
Carlos Gomez-Roca: IUCT, Institut Universitaire du Cancer de Toulouse
Carlos Eduardo Andrea: Clínica Universidad de Navarra
David Spigel: Sarah Cannon Research Institute
Thomas Wu: Genentech
Lelia Delamarre: Genentech
Johannes Schöneberg: UCSD
Zora Modrusan: Genentech
Richard Price: Genentech
Shannon J. Turley: Genentech
Ira Mellman: Genentech
Christine Moussion: Genentech

Nature, 2023, vol. 618, issue 7966, 827-833

Abstract: Abstract The immune phenotype of a tumour is a key predictor of its response to immunotherapy1–4. Patients who respond to checkpoint blockade generally present with immune-inflamed5–7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)—a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06132-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:618:y:2023:i:7966:d:10.1038_s41586-023-06132-2

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

DOI: 10.1038/s41586-023-06132-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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