{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:18:46Z","timestamp":1789525126236,"version":"build-2803163510"},"reference-count":85,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["23-25-00294"],"award-info":[{"award-number":["23-25-00294"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>One of the effective strategies for the treatment of tumor diseases, including colitis-associated colorectal cancer (CAC), is immunotherapy. During inflammation, NF-\u03baB is activated, which is connected with the hypoxia-inducible factor\u2014HIF, regulating the immune cells functioning and influences the CAC development. Organisms differ according to their hypoxia resistance and HIF expression. Therefore, the aim of the study was to characterize the thymus, spleen and mesenteric lymph nodes morphofunctional features, as well as changes in the subpopulation composition of peripheral blood cells and mesenteric lymph nodes in tolerant and susceptible to hypoxia C57Bl\/6 mice in CAC.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>Hypoxia tolerance was assessed by gasping time measurement in hypobaric decompression chamber. Based on the outcome, the mice were assigned to three groups characterized as \u2018tolerant to hypoxia\u2019, \u2018normal\u2019, and \u2018susceptible to hypoxia\u2019. A month after determining hypoxia resistance CAC was modeled by intraperitoneal azoxymethane (AOM) administration and three cycles of dextran sulfate sodium consumption. Mice were sacrificed on the 141st day after the AOM administration, a morphological, morphometric and immunohistochemical study of tumors, morphological and morphometric study of thymus and spleen, and subpopulation composition of peripheral blood cells and mesenteric lymph nodes assessment were carried out.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>Tumors in tolerant and susceptible to hypoxia mice were represented by glandular intraepithelial neoplasia and adenocarcinomas, the area of which was larger in susceptible mice. Immunohistochemical study revealed a more pronounced Ki-67+ staining in tumors of susceptible mice. In CAC, only in tolerant mice, expansion of the thymic cortex was observed relative to the control group, while in susceptible ones, no changes were detected. Only in susceptible to hypoxia mice, spleen germinal centers of lymphoid follicles enlargement were observed. Only in susceptible mice during CAC, in comparison to the control group, the relative and absolute number of B-lymphocytes and relative\u2014cytotoxic T-lymphocytes in blood increased. The relative cytotoxic T-lymphocytes and NK cells number in peripheral blood during CAC was higher in susceptible to hypoxia mice compared to tolerant ones. In susceptible to hypoxia mice, more pronounced changes in the mesenteric lymph nodes subpopulation composition of cells were revealed\u2014only in them the absolute and relative number of B-lymphocytes and NK cells, the absolute number of cytotoxic T-lymphocytes increased, and the relative number of macrophages decreased.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>Morphofunctional differences in the thymus, spleen, mesenteric lymph nodes and blood immune cells reactions indicated the more pronounced immune response to the CAC development in susceptible to hypoxia mice, which should be taken into account in experimental studies.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.19024","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T08:45:32Z","timestamp":1740473132000},"page":"e19024","source":"Crossref","is-referenced-by-count":5,"title":["Morphofunctional changes in the immune system in colitis-associated colorectal cancer in tolerant and susceptible to hypoxia mice"],"prefix":"10.7717","volume":"13","author":[{"given":"Dzhuliia","family":"Dzhalilova","sequence":"first","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Silina","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kosyreva","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, People\u2019s Friendship University of Russia (RUDN University), Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Fokichev","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, Russia"},{"name":"Faculty of Biology and Biotechnology, HSE University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Makarova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"10.7717\/peerj.19024\/ref-1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.semcancer.2011.12.005","article-title":"Cancer-related inflammation: common themes and therapeutic opportunities","volume":"22","author":"Balkwill","year":"2012","journal-title":"Seminars in Cancer Biology"},{"key":"10.7717\/peerj.19024\/ref-2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/imr.12029","article-title":"Metabolic control of the Treg\/Th17 axis","volume":"252","author":"Barbi","year":"2013","journal-title":"Immunological Reviews"},{"key":"10.7717\/peerj.19024\/ref-3","doi-asserted-by":"publisher","first-page":"5373","DOI":"10.1200\/JCO.2006.05.9584","article-title":"Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse","volume":"24","author":"Bates","year":"2006","journal-title":"Journal of Clinical Oncology"},{"issue":"1","key":"10.7717\/peerj.19024\/ref-4","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3390\/biom10010114","article-title":"Transport of Ca2+ and Ca2+-dependent permeability transition in the liver and heart mitochondria of rats with different tolerance to acute hypoxia","volume":"10","author":"Belosludtsev","year":"2020","journal-title":"Biomolecules"},{"key":"10.7717\/peerj.19024\/ref-5","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nature Immunology"},{"key":"10.7717\/peerj.19024\/ref-6","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"10.7717\/peerj.19024\/ref-7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nri2916","article-title":"Phenotypical and functional specialization of FOXP3+ regulatory T cells","volume":"11","author":"Campbell","year":"2011","journal-title":"Nature Reviews. Immunology"},{"key":"10.7717\/peerj.19024\/ref-8","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1158\/0008-5472.CAN-08-2654","article-title":"Coordination of intratumoral immune reaction and human colorectal cancer recurrence","volume":"69","author":"Camus","year":"2009","journal-title":"Cancer Research"},{"key":"10.7717\/peerj.19024\/ref-9","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1136\/gut.2008.158824","article-title":"Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue","volume":"58","author":"Chaput","year":"2009","journal-title":"Gut"},{"key":"10.7717\/peerj.19024\/ref-10","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature19334","article-title":"Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system","volume":"537","author":"Cho","year":"2016","journal-title":"Nature"},{"key":"10.7717\/peerj.19024\/ref-11","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature01326","article-title":"The immunopathogenesis of sepsis","volume":"420","author":"Cohen","year":"2002","journal-title":"Nature"},{"key":"10.7717\/peerj.19024\/ref-12","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1146\/annurev-immunol-100819-121537","article-title":"Hypoxia and innate immunity: keeping up with the HIFsters","volume":"38","author":"Colgan","year":"2020","journal-title":"Annual Review of Immunology"},{"key":"10.7717\/peerj.19024\/ref-13","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"10.7717\/peerj.19024\/ref-14","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1007\/s00262-007-0343-y","article-title":"Dynamic cross-talk between tumor and immune cells in orchestrating the immunosuppressive network at the tumor microenvironment","volume":"56","author":"Croci","year":"2007","journal-title":"Cancer Immunology, Immunotherapy"},{"key":"10.7717\/peerj.19024\/ref-15","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nm1093","article-title":"Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival","volume":"10","author":"Curiel","year":"2004","journal-title":"Nature Medicine"},{"key":"10.7717\/peerj.19024\/ref-16","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1158\/1078-0432.CCR-11-3216","article-title":"The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature","volume":"18","author":"De Leeuw","year":"2012","journal-title":"Clinical Cancer Research"},{"issue":"4","key":"10.7717\/peerj.19024\/ref-17","doi-asserted-by":"publisher","first-page":"726","DOI":"10.3390\/nu14040726","article-title":"Pre-administration of berberine exerts chemopreventive effects in AOM\/DSS-induced colitis-associated carcinogenesis mice via modulating inflammation and intestinal microbiota","volume":"14","author":"Deng","year":"2022","journal-title":"Nutrients"},{"key":"10.7717\/peerj.19024\/ref-18","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1146\/annurev-pathol-012615-044359","article-title":"Obesity, inflammation, and cancer","volume":"11","author":"Deng","year":"2016","journal-title":"Annual Review of Pathology"},{"issue":"7","key":"10.7717\/peerj.19024\/ref-19","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3390\/ijms17071030","article-title":"The immunogenicity of colorectal cancer in relation to tumor development and treatment","volume":"17","author":"De Vries","year":"2016","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.19024\/ref-20","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2147\/JIR.S194581","article-title":"Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats","volume":"12","author":"Dzhalilova","year":"2019","journal-title":"Journal of Inflammation Research"},{"issue":"2019","key":"10.7717\/peerj.19024\/ref-21","doi-asserted-by":"publisher","first-page":"7584685","DOI":"10.1155\/2019\/7584685","article-title":"Morphological characteristics of the thymus and spleen and the subpopulation composition of lymphocytes in peripheral blood during systemic inflammatory response in male rats with different resistance to hypoxia","volume":"2019","author":"Dzhalilova","year":"2019","journal-title":"International Journal of Inflammation"},{"key":"10.7717\/peerj.19024\/ref-22","doi-asserted-by":"publisher","first-page":"46","DOI":"10.29296\/24999490-2018-06-08","article-title":"Morphological changes in the colon and composition of peripheral blood lymphocytes in acute colitis in mice with different resistance to hypoxia","volume":"16","author":"Dzhalilova","year":"2018","journal-title":"Molucca Medica"},{"issue":"14","key":"10.7717\/peerj.19024\/ref-23","doi-asserted-by":"publisher","first-page":"7801","DOI":"10.3390\/ijms25147801","article-title":"Changes in the expression of genes regulating the response to hypoxia, inflammation, cell cycle, apoptosis, and epithelial barrier functioning during colitis-associated colorectal cancer depend on individual hypoxia tolerance","volume":"25","author":"Dzhalilova","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.19024\/ref-24","doi-asserted-by":"publisher","first-page":"413","DOI":"10.46235\/1028-7221-16818-TMC","article-title":"Thymus morphological characteristics in acute and chronic colitis in animals with different hypoxia tolerance","volume":"27","author":"Dzhalilova","year":"2024","journal-title":"Russian Journal of Immunology"},{"key":"10.7717\/peerj.19024\/ref-25","doi-asserted-by":"publisher","first-page":"13","DOI":"10.31088\/2226-5988-2018-28-4-13-20","article-title":"Morphological features of the inflammatory process and subpopulation pattern of peripheral blood lymphocytes during chronic colitis in mice exhibiting different responses to hypoxia","volume":"28","author":"Dzhalilova","year":"2018","journal-title":"Clinical and Experimental Morphology"},{"key":"10.7717\/peerj.19024\/ref-26","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/j.1365-3083.2007.01923.x","article-title":"Dextran sulfate sodium-induced colitis generates a transient thymic involution\u2013impact on thymocyte subsets","volume":"65","author":"Fritsch\u00a0Fredin","year":"2007","journal-title":"Scandinavian Journal of Immunology"},{"key":"10.7717\/peerj.19024\/ref-27","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1126\/science.1129139","article-title":"Type, density, and location of immune cells within human colorectal tumors predict clinical outcome","volume":"313","author":"Galon","year":"2006","journal-title":"Science"},{"key":"10.7717\/peerj.19024\/ref-28","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1200\/JCO.2006.09.4565","article-title":"Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection","volume":"25","author":"Gao","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.19024\/ref-29","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.4049\/jimmunol.133.4.1710","article-title":"Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67","volume":"133","author":"Gerdes","year":"1984","journal-title":"Journal of Immunology"},{"key":"10.7717\/peerj.19024\/ref-30","first-page":"744","article-title":"Individual variation in response to simulated hypoxic stress of rats","volume":"50","author":"Ghosh","year":"2012","journal-title":"Indian Journal of Experimental Biology"},{"key":"10.7717\/peerj.19024\/ref-31","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"10.7717\/peerj.19024\/ref-32","doi-asserted-by":"publisher","first-page":"5423","DOI":"10.1158\/1078-0432.CCR-06-0369","article-title":"Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions","volume":"12","author":"Hiraoka","year":"2006","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.19024\/ref-33","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s12192-014-0504-9","article-title":"Differential hypoxic tolerance is mediated by activation of heat shock response and nitric oxide pathway","volume":"19","author":"Jain","year":"2014","journal-title":"Cell Stress & Chaperones"},{"key":"10.7717\/peerj.19024\/ref-34","doi-asserted-by":"publisher","first-page":"4667","DOI":"10.1016\/j.ijcard.2013.07.180","article-title":"Differential activation of myocardial ER stress response: a possible role in hypoxic tolerance","volume":"168","author":"Jain","year":"2013","journal-title":"International Journal of Cardiology"},{"key":"10.7717\/peerj.19024\/ref-35","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1189\/jlb.1210683","article-title":"Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1\u03b1 (HIF1A) and result in differential HIF1A-dependent gene expression","volume":"90","author":"Jantsch","year":"2011","journal-title":"Journal of Leukocyte Biology"},{"key":"10.7717\/peerj.19024\/ref-36","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1158\/1078-0432.CCR-07-4554","article-title":"Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+\/regulatory T-cell ratio: which variable determines survival of cervical cancer patients?","volume":"14","author":"Jordanova","year":"2008","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.19024\/ref-37","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.semcancer.2012.02.008","article-title":"New insights into chronic inflammation-induced immunosuppression","volume":"22","author":"Kanterman","year":"2012","journal-title":"Seminars in Cancer Biology"},{"key":"10.7717\/peerj.19024\/ref-38","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1007\/s10517-013-2038-z","article-title":"Phenotypic features of the dynamics of HIF-1\u03b1 levels in rat neocortex in different hypoxia regimens","volume":"154","author":"Kirova","year":"2013","journal-title":"Bulletin of Experimental Biology and Medicine"},{"key":"10.7717\/peerj.19024\/ref-39","doi-asserted-by":"publisher","first-page":"15884","DOI":"10.1038\/s41598-020-72537-y","article-title":"Sex differences of inflammatory and immune response in pups of Wistar rats with SIRS","volume":"10","author":"Kosyreva","year":"2020","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.19024\/ref-40","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/s00262-011-1046-y","article-title":"Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer","volume":"60","author":"Ladoire","year":"2011","journal-title":"Cancer Immunology, Immunotherapy"},{"key":"10.7717\/peerj.19024\/ref-41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.semcancer.2023.04.008","article-title":"Obesity-induced thymic involution and cancer risk","volume":"93","author":"Lagou","year":"2023","journal-title":"Seminars in Cancer Biology"},{"key":"10.7717\/peerj.19024\/ref-42","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.1007\/s00262-021-02859-x","article-title":"CD30+OX40+ Treg is associated with improved overall survival in colorectal cancer","volume":"70","author":"Lam","year":"2021","journal-title":"Cancer Immunology, Immunotherapy"},{"issue":"1","key":"10.7717\/peerj.19024\/ref-43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3390\/cells10010100","article-title":"Inflammatory cytokines in cancer: comprehensive understanding and clinical progress in gene therapy","volume":"10","author":"Lan","year":"2021","journal-title":"Cell"},{"key":"10.7717\/peerj.19024\/ref-44","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/ni.3384","article-title":"Inflammatory networks underlying colorectal cancer","volume":"17","author":"Lasry","year":"2016","journal-title":"Nature Immunology"},{"key":"10.7717\/peerj.19024\/ref-45","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1464-410X.2008.08151.x","article-title":"The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma","volume":"103","author":"Li","year":"2009","journal-title":"BJU International"},{"key":"10.7717\/peerj.19024\/ref-46","doi-asserted-by":"publisher","first-page":"104409","DOI":"10.1016\/j.cellimm.2021.104409","article-title":"Regulation of humoral immune response by HIF-1\u03b1-dependent metabolic reprogramming of the germinal center reaction","volume":"367","author":"Li","year":"2021","journal-title":"Cellular Immunology"},{"key":"10.7717\/peerj.19024\/ref-47","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s12967-024-05104-y","article-title":"Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review","volume":"22","author":"Li","year":"2024","journal-title":"Journal of Translational Medicine"},{"key":"10.7717\/peerj.19024\/ref-48","doi-asserted-by":"publisher","first-page":"7506","DOI":"10.3892\/ol.2018.8355","article-title":"Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases","volume":"15","author":"Li","year":"2018","journal-title":"Oncology Letters"},{"key":"10.7717\/peerj.19024\/ref-49","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1038\/bjc.2014.161","article-title":"The intratumoural subsite and relation of CD8(+) and FOXP3(+) T lymphocytes in colorectal cancer provide important prognostic clues","volume":"110","author":"Ling","year":"2014","journal-title":"British Journal of Cancer"},{"key":"10.7717\/peerj.19024\/ref-50","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1007\/s00418-008-0530-8","article-title":"The tumor microenvironment and its contribution to tumor evolution toward metastasis","volume":"130","author":"Lorusso","year":"2008","journal-title":"Histochemistry and Cell Biology"},{"key":"10.7717\/peerj.19024\/ref-51","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.cmet.2020.08.002","article-title":"The role of HIF in immunity and inflammation","volume":"32","author":"McGettrick","year":"2020","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.19024\/ref-52","doi-asserted-by":"publisher","first-page":"e15366","DOI":"10.1371\/journal.pone.0015366","article-title":"The inflammatory microenvironment in colorectal neoplasia","volume":"6","author":"McLean","year":"2011","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.19024\/ref-53","doi-asserted-by":"publisher","first-page":"G1328","DOI":"10.1152\/ajpgi.00467.2004","article-title":"Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL\/6 but not in BALB\/c mice: correlation between symptoms and inflammation","volume":"288","author":"Melgar","year":"2005","journal-title":"American Journal of Physiology. Gastrointestinal and Liver Physiology"},{"key":"10.7717\/peerj.19024\/ref-54","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s10863-019-09806-7","article-title":"Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage","volume":"51","author":"Mironova","year":"2019","journal-title":"Journal of Bioenergetics and Biomembranes"},{"key":"10.7717\/peerj.19024\/ref-55","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1200\/JCO.2010.30.5425","article-title":"Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction","volume":"29","author":"Mlecnik","year":"2011","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.19024\/ref-56","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12199-018-0740-1","article-title":"Inflammation and cancer","volume":"23","author":"Murata","year":"2018","journal-title":"Environmental Health and Preventive Medicine"},{"issue":"9","key":"10.7717\/peerj.19024\/ref-57","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.3390\/cancers15092570","article-title":"Experimental murine models for colorectal cancer research","volume":"15","author":"Neto","year":"2023","journal-title":"Cancer"},{"key":"10.7717\/peerj.19024\/ref-58","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1038\/s41590-019-0415-0","article-title":"Targeting immune cell circuits and trafficking in inflammatory bowel disease","volume":"20","author":"Neurath","year":"2019","journal-title":"Nature Immunology"},{"key":"10.7717\/peerj.19024\/ref-59","doi-asserted-by":"publisher","first-page":"3540","DOI":"10.1158\/0008-5472.CAN-11-0096","article-title":"Anti-TIM3 antibody promotes T cell IFN-\u03b3-mediated antitumor immunity and suppresses established tumors","volume":"71","author":"Ngiow","year":"2011","journal-title":"Cancer Research"},{"key":"10.7717\/peerj.19024\/ref-60","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.imlet.2020.03.001","article-title":"The link Cancer and autoimmune diseases in the light of microbiota: evidence of a potential culprit","volume":"222","author":"Niccolai","year":"2020","journal-title":"Immunology Letters"},{"key":"10.7717\/peerj.19024\/ref-61","doi-asserted-by":"publisher","first-page":"239","DOI":"10.7150\/jca.21336","article-title":"Early and partial reduction in CD4+Foxp3+ regulatory T cells during colitis-associated colon cancer induces CD4+ and CD8+ T cell activation inhibiting tumorigenesis","volume":"9","author":"Olgu\u00edn","year":"2018","journal-title":"Journal of Cancer"},{"key":"10.7717\/peerj.19024\/ref-62","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1089\/ham.2012.1095","article-title":"Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure","volume":"14","author":"Padhy","year":"2013","journal-title":"High Altitude Medicine & Biology"},{"key":"10.7717\/peerj.19024\/ref-63","doi-asserted-by":"publisher","first-page":"5944","DOI":"10.1200\/JCO.2008.19.6147","article-title":"In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer","volume":"27","author":"Pag\u00e8s","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.19024\/ref-64","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1007\/s10517-018-3993-1","article-title":"Specific features of immediate ultrastructural changes in brain cortex mitochondria of rats with different tolerance to hypoxia under various modes of hypoxic exposures","volume":"164","author":"Pavlik","year":"2018","journal-title":"Bulletin of Experimental Biology and Medicine"},{"key":"10.7717\/peerj.19024\/ref-65","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1111\/imr.12726","article-title":"Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms","volume":"287","author":"Pazmandi","year":"2019","journal-title":"Immunological Reviews"},{"key":"10.7717\/peerj.19024\/ref-66","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/j.ejca.2008.05.017","article-title":"Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer","volume":"44","author":"Perrone","year":"2008","journal-title":"European Journal of Cancer"},{"key":"10.7717\/peerj.19024\/ref-67","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1002\/cncr.22282","article-title":"Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients","volume":"107","author":"Petersen","year":"2006","journal-title":"Cancer"},{"key":"10.7717\/peerj.19024\/ref-68","doi-asserted-by":"publisher","first-page":"53","DOI":"10.17116\/patol20198105153","article-title":"Morphology of the thymus and the specific features of its cellular composition in experimental acute and chronic ulcerative colitis","volume":"81","author":"Postovalova","year":"2019","journal-title":"Arkhiv Patologii"},{"key":"10.7717\/peerj.19024\/ref-69","doi-asserted-by":"publisher","first-page":"53","DOI":"10.17116\/patol20198105153","article-title":"Morphology of the thymus and the specific features of its cellular composition in experimental acute and chronic ulcerative colitis","volume":"81","author":"Postovalova","year":"2019","journal-title":"Russian Journal of Archive of Patology"},{"key":"10.7717\/peerj.19024\/ref-70","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/bs.ircmb.2018.08.001","article-title":"Cancer immunosurveillance by T cells","volume":"342","author":"Rao","year":"2019","journal-title":"International Review of Cell and Molecular Biology"},{"key":"10.7717\/peerj.19024\/ref-71","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/nature06905","article-title":"NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha","volume":"453","author":"Rius","year":"2008","journal-title":"Nature"},{"key":"10.7717\/peerj.19024\/ref-72","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1200\/JCO.2008.18.7229","article-title":"Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer","volume":"27","author":"Salama","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.19024\/ref-73","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s10753-008-9081-3","article-title":"Thymic involution correlates with severe ulcerative colitis induced by oral administration of dextran sulphate sodium in C57BL\/6 mice but not in BALB\/c mice","volume":"31","author":"Sasaki","year":"2008","journal-title":"Inflammation"},{"key":"10.7717\/peerj.19024\/ref-74","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1158\/2326-6066.CIR-19-0567","article-title":"Impact of TCR diversity on the development of transplanted or chemically induced tumors","volume":"8","author":"Schreiber","year":"2020","journal-title":"Cancer Immunology Research"},{"key":"10.7717\/peerj.19024\/ref-75","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/j.imbio.2015.06.003","article-title":"Changes of immunocytic phenotypes and functions from human colorectal adenomatous stage to cancerous stage: update","volume":"220","author":"Shi","year":"2015","journal-title":"Immunobiology"},{"issue":"1","key":"10.7717\/peerj.19024\/ref-76","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3892\/ol.2020.12268","article-title":"Long-term model of colitis-associated colorectal cancer suggests tumor spread mechanism and nature of cancer stem cells","volume":"21","author":"Tanimura","year":"2021","journal-title":"Oncology Letters"},{"key":"10.7717\/peerj.19024\/ref-77","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/s41581-022-00587-8","article-title":"The effect of HIF on metabolism and immunity","volume":"18","author":"Taylor","year":"2022","journal-title":"Nature Reviews. Nephrology"},{"key":"10.7717\/peerj.19024\/ref-78","doi-asserted-by":"publisher","first-page":"336","DOI":"10.33594\/000000716","article-title":"Elucidation of the role of L-Arginine and N\u03c9-Nitro-L-Arginine in the treatment of rats with different levels of hypoxic tolerance and exposure to lead nitrate","volume":"58","author":"Tkaczenko","year":"2024","journal-title":"Cellular Physiology and Biochemistry"},{"key":"10.7717\/peerj.19024\/ref-79","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1042\/BJ20080476","article-title":"Regulation of hypoxia-inducible factor-1alpha by NF-kappaB","volume":"412","author":"Van Uden","year":"2008","journal-title":"The Biochemical Journal"},{"key":"10.7717\/peerj.19024\/ref-80","doi-asserted-by":"publisher","first-page":"e1001285","DOI":"10.1371\/journal.pgen.1001285","article-title":"Evolutionary conserved regulation of HIF-1\u03b2 by NF-\u03baB","volume":"7","author":"Van Uden","year":"2011","journal-title":"PLOS Genetics"},{"key":"10.7717\/peerj.19024\/ref-81","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1093\/carcin\/bgv123","article-title":"Immunosuppression associated with chronic inflammation in the tumor microenvironment","volume":"36","author":"Wang","year":"2015","journal-title":"Carcinogenesis"},{"key":"10.7717\/peerj.19024\/ref-82","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3389\/fimmu.2020.00773","article-title":"Thymic Function associated with cancer development, relapse, and antitumor immunity\u2014a mini-review","volume":"11","author":"Wang","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"10.7717\/peerj.19024\/ref-83","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nri3896","article-title":"Emerging cytokine networks in colorectal cancer","volume":"15","author":"West","year":"2015","journal-title":"Nature Reviews. Immunology"},{"key":"10.7717\/peerj.19024\/ref-84","doi-asserted-by":"publisher","first-page":"372","DOI":"10.3390\/gidisord1040030","article-title":"Cytomorphological characterization of individual metastatic tumor cells from gastrointestinal cancer patient lymph nodes with imaging flow cytometry","volume":"1","author":"Winter","year":"2019","journal-title":"Gastrointestinal Disorders"},{"key":"10.7717\/peerj.19024\/ref-85","doi-asserted-by":"publisher","first-page":"1338918","DOI":"10.3389\/fimmu.2023.1338918","article-title":"Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota","volume":"14","author":"Zhang","year":"2023","journal-title":"Frontiers in Immunology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/19024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19024.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19024.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T08:45:44Z","timestamp":1740473144000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/19024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":85,"alternative-id":["10.7717\/peerj.19024"],"URL":"https:\/\/doi.org\/10.7717\/peerj.19024","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"article-number":"e19024"}}