Document Type
Article
Publication Date
9-28-2024
Original Citation
Wang V,
Liu Z,
Martinek J,
Foroughi Pour A,
Zhou J,
Boruchov H,
Ray K,
Palucka K,
Chuang J.
Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments. Commun Biol. 2024;7(1):1201.
Keywords
JGM, Humans, Tumor Microenvironment, T-Lymphocytes, Immunological Synapses, Melanoma, Cell Communication, Computational Biology, Female, Breast Neoplasms
JAX Source
Commun Biol. 2024;7(1):1201.
ISSN
2399-3642
PMID
39341903
DOI
https://doi.org/10.1038/s42003-024-06902-2
Grant
All authors acknowledge support from NIH grants P30CA034196 and R01CA219880. V.G.W., Z.L., A.F.P., J.Z., and J.H.C. acknowledge support from R21CA191848, R01CA230031. J.M. and K.P. acknowledge support from R01CA204115 and R01CA195712.
Abstract
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.