Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
28 Sep 2024
28 Sep 2024
Historique:
received:
11
03
2024
accepted:
16
09
2024
medline:
29
9
2024
pubmed:
29
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect T-cell:APC (antigen presenting cell) synaptic interactions in two independent human melanoma imaging mass cytometry (IMC) tissue microarray datasets. We then verify CISA's applicability across data modalities with melanoma histocytometry whole slide images, revealing that T-cell:macrophage synapse formation correlates with T-cell proliferation. We next show the generality of CISA by extending it to breast cancer IMC images, finding that CISA quantifications of T-cell:B-cell synapses are predictive of improved patient survival. Our work demonstrates the biological and clinical significance of spatially resolving cell-cell synaptic interactions in the TME and provides a robust method to do so across imaging modalities and cancer types.
Identifiants
pubmed: 39341903
doi: 10.1038/s42003-024-06902-2
pii: 10.1038/s42003-024-06902-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1201Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA034196
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01CA230031
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01CA204115
Informations de copyright
© 2024. The Author(s).
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