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In this study, we compared the composition and prognostic significance of the immune microenvironment in lung metastases, paired primary tumors, and liver metastases from a retrospective cohort of 216 patients with metastatic CRC who underwent pulmonary metastasectomy in a single Swedish institution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immunohistochemistry was applied on tissue microarrays to evaluate CD3\n                      <jats:sup>+<\/jats:sup>\n                      , CD8\n                      <jats:sup>+<\/jats:sup>\n                      , CD20\n                      <jats:sup>+<\/jats:sup>\n                      , FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      immune cells, PD\u2010L1\n                      <jats:sup>+<\/jats:sup>\n                      immune cells and tumor cells, and tertiary lymphoid\u2010like structures (TLLS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lung metastases exhibited significantly higher infiltration of all immune cell subsets compared to both primary tumors and liver metastases. FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      cell density was lower in liver metastases than in primary tumors. Immune cell infiltration in lung metastases was largely unaffected by neoadjuvant chemotherapy, except for lower FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      cell infiltration in treated cases. None of the immune markers bore prognostic significance in the overall analysis. However, high infiltration of FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      , CD20\n                      <jats:sup>+<\/jats:sup>\n                      , and PD\u2010L1\n                      <jats:sup>+<\/jats:sup>\n                      immune cells, and presence of TLLSs in lung metastases were associated with improved overall survival in patients receiving adjuvant chemotherapy, with a significant prognostic treatment interaction. None of the immune markers were prognostic in primary tumors or liver metastases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscore a distinct, more immunologically active immune microenvironment in CRC lung metastases compared to primary tumors and liver metastases, that suggestedly also predicts response to adjuvant chemotherapy. Immune profiling of lung metastases may thus pave the way for improved personalized treatment of these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71739","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:13:51Z","timestamp":1773994431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor\u2010Infiltrating Immune Cells Are More Abundant in Lung Metastases From Colorectal Cancer Than in Paired Primary Tumors and Their Prognostic Value Depends on Adjuvant Chemotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Danyil","family":"Kuznyecov","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund, Division of Oncology and Therapeutic Pathology Lund University  Lund Sweden"},{"name":"Department of Clinical Genetics, Pathology and Molecular Diagnostics Sk\u00e5ne University Hospital  Lund 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