{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:40:56Z","timestamp":1793814056024,"version":"4.6.1"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20ZR1409000"],"award-info":[{"award-number":["20ZR1409000"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31570803"],"award-info":[{"award-number":["31570803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773090"],"award-info":[{"award-number":["81773090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072881"],"award-info":[{"award-number":["82072881"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015310","name":"Natural Science Foundation of Xinjiang","doi-asserted-by":"publisher","award":["2019D01C088"],"award-info":[{"award-number":["2019D01C088"]}],"id":[{"id":"10.13039\/501100015310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Deciphering the determinants of the intralesional immune reaction in cervical carcinogenesis may be conducive to improving the understanding of the disease and then improve outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public gene\u2010expression data and full clinical annotation were searched in Gene Expression Omnibus in the joint analysis of the array\u2010based four eligible cohorts. The infiltrating estimation was quantified using microenvironment cell populations\u2010counter algorithm and absolute\u2010mode CIBERSORT and verified by flow cytometry analysis. An unsupervised classification on immune genes strongly associated with progression, designated by linear mixed\u2010effects regression. We determined immune response and signaling features of the different developmental stages and immune phenotypes by functional annotation and systematically correlated the expression of immune checkpoints with cell\u2010infiltrating characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified the lesion\u2010intrinsic immunosuppression mechanism was triggered at precancerous stages, such as genome instability and mutation, aerobic glycolysis, activation of proto\u2010oncogene pathways and so forth. Predominant innate and adoptive cells were increasing from normalcy to cancer (B cell, total T cell, regulatory T cells [Tregs], monocytes, neutrophils, and M2\u2010like macrophages) together with the decrease of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell through the development of cervical cancer. Immune escape initiated on the expression of immunosuppressive molecules from high\u2010grade squamous intraepithelial lesions (HSIL) and culminated in squamous cell carcinoma (SCC). Of note, the expression of immune checkpoints was escalated in the immune\u2010hot and immune\u2010warm phenotype largely encompassed by HSIL and SCC under the stress of both activated and suppressive immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Immune surveillance is unleashing from low\u2010grade squamous intraepithelial lesions onwards and immune\u2010suppression mechanisms are triggered in HSIL. Thorough knowledge of the immune changing pattern during cervical tumorigenesis contributes to finding the potential therapeutic targets to susceptive patients towards immune checkpoints inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.3833","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T01:30:42Z","timestamp":1615426242000},"page":"2380-2395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The immune landscape during the tumorigenesis of cervical cancer"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9661-6111","authenticated-orcid":false,"given":"Yiying","family":"Wang","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital Fudan University Shanghai China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2693-5261","authenticated-orcid":false,"given":"Mengdi","family":"He","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-1335","authenticated-orcid":false,"given":"Guodong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9242-1440","authenticated-orcid":false,"given":"Kankan","family":"Cao","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital Fudan University Shanghai 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