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Recent evidence indicates that neoadjuvant immunotherapy can be used to treat pMMR CRC before surgery, potentially reducing postoperative relapse. Tan\n                    <jats:italic>et\u00a0al<\/jats:italic>\n                    . report results from the NICHE\u20102 trial, which achieved a 26% response rate in early\u2010stage pMMR colon cancer (CC) patients. Molecular studies show that despite low tumor mutational burden (TMB), responders exhibit higher chromosomal instability (CIN), TP53 mutations, and enrichment of proliferative and cell\u2010cycle signatures, associated with higher density of Ki\u201067\n                    <jats:sup>+<\/jats:sup>\n                    tumor and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells. In contrast, nonresponders display metabolic and stromal reprogramming, enhanced TGF\u2010\u03b2 signaling, and immune exclusion. Circulating tumor DNA (ctDNA) clearance correlated with pathological response and long\u2010term disease\u2010free survival postsurgery. While the biological and molecular determinants underlying the response rates observed in the NICHE\u20102 trial remain to be fully elucidated, the work by Tan et\u00a0al. suggests that biomarker\u2010guided neoadjuvant immunotherapy could represent a valuable strategy to achieve pathological responses in early\u2010stage pMMR CC, despite its clinical relevance requiring further evaluation.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70178","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T07:25:12Z","timestamp":1764573912000},"page":"579-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A subset of\n                    <scp>MMR<\/scp>\n                    \u2010proficient colon cancers responds to neoadjuvant immunotherapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Eleonora","family":"Piumatti","sequence":"first","affiliation":[{"name":"Department of 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