{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:04:23Z","timestamp":1790168663536,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Research Council, the Swedish Cancer Society and the Swedish state under the ALF agreement","award":["ALFGBG-965932"],"award-info":[{"award-number":["ALFGBG-965932"]}]},{"name":"Bengt Ihre Foundation and the Swedish state under the ALF agreement","award":["ALFGBG-965932"],"award-info":[{"award-number":["ALFGBG-965932"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The incidence of left-sided colon and rectal cancer in young people are increasing worldwide, but its causes are poorly understood. It is not clear if the tumor microenvironment is dependent on age of onset, and little is known about the composition of tumor-infiltrating T cells in early-onset colorectal cancer (EOCRC). To address this, we investigated T-cell subsets and performed gene expression immune profiling in sporadic EOCRC tumors and matched average-onset colorectal cancer (AOCRC) tumors. Left-sided colon and rectal tumors from 40 cases were analyzed; 20 EOCRC (&lt;45 years) patients were matched 1:1 to AOCRC (70\u201375 years) patients by gender, tumor location, and stage. Cases with germline pathogenic variants, inflammatory bowel disease or neoadjuvant-treated tumors were excluded. For T cells in tumors and stroma, a multiplex immunofluorescence assay combined with digital image analysis and machine learning algorithms was used. Immunological mediators in the tumor microenvironment were assessed by NanoString gene expression profiling of mRNA. Immunofluorescence revealed no significant difference between EOCRC and AOCRC with regard to infiltration of total T cells, conventional CD4+ and CD8+ T cells, regulatory T cells, or \u03b3\u03b4 T cells. Most T cells were located in the stroma in both EOCRC and AOCRC. Immune profiling by gene expression revealed higher expression in AOCRC of the immunoregulatory cytokine IL-10, the inhibitory NK cell receptors KIR3DL3 and KLRB1 (CD161), and IFN-a7 (IFNA7). In contrast, the interferon-induced gene IFIT2 was more highly expressed in EOCRC. However, in a global analysis of 770 tumor immunity genes, no significant differences could be detected. T-cell infiltration and expression of inflammatory mediators are similar in EOCRC and AOCRC. This may indicate that the immune response to cancer in left colon and rectum is not related to age of onset and that EOCRC is likely not driven by immune response deficiency.<\/jats:p>","DOI":"10.3390\/cancers15051457","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:04:11Z","timestamp":1677463451000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Immune Microenvironment in Sporadic Early-Onset versus Average-Onset Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Fanny","family":"Andric","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Al-Fairouzi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8660-7169","authenticated-orcid":false,"given":"Yvonne","family":"Wettergren","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Szeponik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-1486","authenticated-orcid":false,"given":"Elinor","family":"Bexe-Lindskog","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"},{"name":"Department of Surgery, Sahlgrenska University Hospital, Region V\u00e4stra G\u00f6taland, 413 45 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"James C.","family":"Cusack","sequence":"additional","affiliation":[{"name":"Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-5405","authenticated-orcid":false,"given":"Gerald","family":"Tumusiime","sequence":"additional","affiliation":[{"name":"Department of Surgery, Uganda Christian University School of Medicine, Mukono P.O. Box 4, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-8091","authenticated-orcid":false,"given":"Marianne","family":"Quiding-J\u00e4rbrink","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-1118","authenticated-orcid":false,"given":"David","family":"Ljungman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden"},{"name":"Department of Surgery, Sahlgrenska University Hospital, Region V\u00e4stra G\u00f6taland, 413 45 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41575-019-0189-8","article-title":"Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies","volume":"16","author":"Keum","year":"2019","journal-title":"Nat. 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