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(DDLS)","award":["2017.0003"],"award-info":[{"award-number":["2017.0003"]}]},{"name":"Data-Driven Life Science (DDLS)","award":["2020.0239"],"award-info":[{"award-number":["2020.0239"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57\u2212) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.<\/jats:p>","DOI":"10.3390\/cancers16132289","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:33:28Z","timestamp":1718948008000},"page":"2289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Lavanya","family":"Lokhande","sequence":"first","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6214-198X","authenticated-orcid":false,"given":"Daniel","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"de Matos Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-0295","authenticated-orcid":false,"given":"Lina M.","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7651-883X","authenticated-orcid":false,"given":"Paul-Theodor","family":"Pyl","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louella","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Porwit","sequence":"additional","affiliation":[{"name":"Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-0365","authenticated-orcid":false,"given":"Anna Sandstr\u00f6m","family":"Gerdtsson","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Jerkeman","sequence":"additional","affiliation":[{"name":"Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-4912","authenticated-orcid":false,"given":"Sara","family":"Ek","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1182\/blood.V124.21.494.494","article-title":"The Tumor Microenvironment in Mantle Cell Lymphoma (MCL): Novel Targets to Overcome Chemo-Resistance in MCL","volume":"124","author":"Pham","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1182\/blood-2019-130512","article-title":"Tumor Microenvironment Molecular Signatures That Define Therapeutic Resistance in Mantle Cell Lymphoma","volume":"134","author":"Nomie","year":"2019","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3324\/haematol.2015.139493","article-title":"Role of the tumor microenvironment in mature B-cell lymphoid malignancies","volume":"101","author":"Fowler","year":"2016","journal-title":"Haematologica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13045-021-01134-x","article-title":"Targeting the tumor microenvironment in B-cell lymphoma: Challenges and opportunities","volume":"14","author":"Liu","year":"2021","journal-title":"J. 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