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Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion beam imaging that produces interpretable results, and is generalizable to other cancer types.<\/jats:p>","DOI":"10.1038\/s42003-021-02361-1","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T06:02:44Z","timestamp":1625810564000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer"],"prefix":"10.1038","volume":"4","author":[{"given":"Aalok","family":"Patwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-2333","authenticated-orcid":false,"given":"Rikiya","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Risom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-5067","authenticated-orcid":false,"given":"Michael","family":"Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leeat","family":"Keren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-4369","authenticated-orcid":false,"given":"Daniel L.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"2361_CR1","unstructured":"Aysola, K. et al. 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