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Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20\u00a0000 patients and\u2009~212\u00a0000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.<\/jats:p>","DOI":"10.1093\/bib\/bbac118","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T12:16:52Z","timestamp":1647001012000},"source":"Crossref","is-referenced-by-count":70,"title":["Comprehensive assessment of cellular senescence in the tumor microenvironment"],"prefix":"10.1093","volume":"23","author":[{"given":"Xiaoman","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Lifei","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Xiaoya","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Heping","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Xiaoqiang","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China"}]},{"given":"Jian-Fei","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Yang-Nan","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Siyao","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Zi-Yu","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Hui-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Xiaoyue","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"given":"Gong-Hong","family":"Wei","sequence":"additional","affiliation":[{"name":"Fudan University Shanghai Cancer Center, Department of Biochemistry and Molecular Biology & Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China"}]},{"given":"De-Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-3182","authenticated-orcid":false,"given":"Hou-Zao","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union 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