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Furthermore, potential markers that can be used to identify responding patients and to further improve efficacy have not been fully explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In our study, we included a total of 97 patients with mCRC, who each received programmed death\u20101 (PD\u20101) inhibitor\u2010based combination therapy at our center. All 12 hypermutated patients benefited from immunotherapy, with median progression\u2010free survival (mPFS) reaching 28.3 months, regardless of liver metastasis. The objective response rate (ORR) of non\u2010hypermutated patients was 16.5% (14\/85), with an mPFS of 4.0 months. For non\u2010hypermutated patients, multivariate analysis revealed that the combination of liver metastasis and baseline lesion number significantly stratified response and survival. The lesion\u2010based analysis indicated that the lymph node was the most responsive, followed by the peritoneum and lung, with liver metastasis being the least responsive. None of the patients (0\/7) with negative programmed ligand\u20101 (PD\u2010L1) expression responded, and positive PD\u2010L1 expression may serve as a biomarker (mPFS 5.7 vs. 2.2 months, <jats:italic>p<\/jats:italic> = 0.002) that can be used to further guide treatment in non\u2010hypermutated mCRC with liver metastasis (CRLMs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with hypermutated mCRC benefited significantly from immunotherapy, whereas the non\u2010hypermutated cohort with liver metastasis and numerous lesions showed less benefit. The lesion sites reflected varying levels of efficacy, among which PD\u2010L1 potentially cooperated to guide the immunotherapy of CRLMs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5959","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T05:24:14Z","timestamp":1682054654000},"page":"12482-12494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metastatic sites and lesion numbers cooperated to predict efficacy of <scp>PD<\/scp>\u20101 inhibitor\u2010based combination therapy for patients with metastatic colorectal cancer"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-8835","authenticated-orcid":false,"given":"Weiqin","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 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