{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:27:20Z","timestamp":1788672440546,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T00:00:00Z","timestamp":1630800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAR 2017\u20132020","award":["FAR 2017\u20132020"],"award-info":[{"award-number":["FAR 2017\u20132020"]}]},{"name":"Fondazione Gigi &amp; Pupa Ferrari Onlus","award":["Fondazione Gigi & Pupa Ferrari Onlus"],"award-info":[{"award-number":["Fondazione Gigi & Pupa Ferrari Onlus"]}]},{"name":"Regione Lombardia POR FESR 2014-2020","award":["Call HUB Ricerca ed Innovazione: ImmunHUB"],"award-info":[{"award-number":["Call HUB Ricerca ed Innovazione: ImmunHUB"]}]},{"DOI":"10.13039\/501100009882","name":"Regione Lombardia","doi-asserted-by":"publisher","award":["programma degli interventi per la ripresa economica: sviluppo di nuovi accordi di collabora-zione con le universit\u00e0 per la ricerca, l'innovazione e il trasferimento tecnologico"],"award-info":[{"award-number":["programma degli interventi per la ripresa economica: sviluppo di nuovi accordi di collabora-zione con le universit\u00e0 per la ricerca, l'innovazione e il trasferimento tecnologico"]}],"id":[{"id":"10.13039\/501100009882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Predicting the prognosis of colorectal cancer (CRC) patients remains challenging and a characterisation of the tumour immune environment represents one of the most crucial avenues when attempting to do so. For this reason, molecular approaches which are capable of classifying the immune environments associated with tumour infiltrating lymphocytes (TILs) are being readily investigated. In this proof of concept study, we aim to explore the feasibility of using spatial lipidomics by MALDI-MSI to distinguish CRC tissue based upon their TIL content. Formalin-fixed paraffin-embedded tissue from human thymus and tonsil was first analysed by MALDI-MSI to obtain a curated mass list from a pool of single positive T lymphocytes, whose putative identities were annotated using an LC-MS-based lipidomic approach. A CRC tissue microarray (TMA, n = 30) was then investigated to determine whether these cases could be distinguished based upon their TIL content in the tumour and its microenvironment. MALDI-MSI from the pool of mature T lymphocytes resulted in the generation of a curated mass list containing 18 annotated m\/z features. Initially, subsets of T lymphocytes were then distinguished based on their state of maturation and differentiation in the human thymus and tonsil tissue. Then, when applied to a CRC TMA containing differing amounts of T lymphocyte infiltration, those cases with a high TIL content were distinguishable from those with a lower TIL content, especially within the tumour microenvironment, with three lipid signals being shown to have the greatest impact on this separation (p &lt; 0.05). On the whole, this preliminary study represents a promising starting point and suggests that a lipidomics MALDI-MSI approach could be a promising tool for subtyping the diverse immune environments in CRC.<\/jats:p>","DOI":"10.3390\/metabo11090599","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:18:26Z","timestamp":1630934306000},"page":"599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6373-689X","authenticated-orcid":false,"given":"Vanna","family":"Denti","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4450-8514","authenticated-orcid":false,"given":"Allia","family":"Mahajneh","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8178-2440","authenticated-orcid":false,"given":"Giulia","family":"Capitoli","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3494-251X","authenticated-orcid":false,"given":"Francesca","family":"Clerici","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-2493","authenticated-orcid":false,"given":"Isabella","family":"Piga","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-932X","authenticated-orcid":false,"given":"Lisa","family":"Pagani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clizia","family":"Chinello","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-2369","authenticated-orcid":false,"given":"Maddalena Maria","family":"Bolognesi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Anatomy and Pathology, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Paglia","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-7242","authenticated-orcid":false,"given":"Stefania","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8663-0374","authenticated-orcid":false,"given":"Fulvio","family":"Magni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-6113","authenticated-orcid":false,"given":"Andrew","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.csbj.2018.11.004","article-title":"Fates of CD8+ T cells in 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