{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:29:00Z","timestamp":1788514140524,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["SUBZ.A412.24.043"],"award-info":[{"award-number":["SUBZ.A412.24.043"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["\u201eWroVasc \u2013 Integrated Cardiovascular Centre\u201d"],"award-info":[{"award-number":["\u201eWroVasc \u2013 Integrated Cardiovascular Centre\u201d"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Minimally invasive surgery is known to lessen postoperative stress and complications compared with open procedures, yet its molecular effects on immunity and cancer-related mechanisms remain unclear. This study examined immune and inflammatory responses after robot-assisted (RS) versus open (OS) colorectal cancer surgery. Sixty-one patients (RS = 30; OS = 31) were enrolled. Blood samples were collected before surgery and at 8, 24, and 72 h post-incision. Cytokines, growth factors, and prostanoids were measured using multiplex immunoassays and mass spectrometry to assess systemic immune and inflammatory changes. Surgery type markedly influenced perioperative immune profiles. RS induced stronger activation of Th1-associated cytokines, including IFN\u03b3 and IP-10, suggesting enhanced cellular immune responsiveness. In contrast, Th2 cytokines and other immunosuppressive mediators\u2014such as IL-4, IL-10, and G-CSF\u2014showed smaller or transient increases after RS, whereas OS triggered broader and more sustained elevations. Angiogenic factors (VEGF-A, PDGF-BB, FGF2) rose significantly after OS but remained comparatively lower and returned to baseline faster after RS, indicating a weaker proangiogenic response. Similarly, postoperative surges in prostaglandins linked to inflammation and tumor progression (PGE2, PGF2\u03b1) were blunted and resolved earlier following RS. Overall, the robotic approach was associated with reduced inflammatory and immunosuppressive activity, faster recovery of immune balance, and diminished biochemical signals favoring angiogenesis and potential tumor regrowth, suggesting a potential protective effect against pathogens and cancer-promoting mechanisms after colorectal tumor resection.<\/jats:p>","DOI":"10.3390\/ijms262010041","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"10041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Robot-Assisted Colorectal Cancer Surgery Mitigates Early Postoperative Immunosuppression and Angiogenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-327X","authenticated-orcid":false,"given":"Mariusz G.","family":"Fleszar","sequence":"first","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Zawadzki","sequence":"additional","affiliation":[{"name":"Department of Oncological Surgery, Regional Specialist Hospital, 51-124 Wroclaw, Poland"},{"name":"Department of Clinical Surgical Sciences, Faculty of Medicine, Wroclaw University of Science and Technology, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4617-798X","authenticated-orcid":false,"given":"Paulina","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-2017","authenticated-orcid":false,"given":"Iwona","family":"Bednarz-Misa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1516-1603","authenticated-orcid":false,"given":"Izabela","family":"Krauze","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Maciejewska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8017-9730","authenticated-orcid":false,"given":"Jakub","family":"Klekowski","sequence":"additional","affiliation":[{"name":"Department of Nursing and Obstetrics, Division of Anesthesiological and Surgical Nursing, Faculty of Health Science, Wroclaw Medical University, 50-367 Wroclaw, Poland"},{"name":"Department of Surgery, 4th Military Clinical Hospital, 50-981 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9232-4525","authenticated-orcid":false,"given":"Mariusz","family":"Chabowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Surgical Sciences, Faculty of Medicine, Wroclaw University of Science and Technology, 50-556 Wroclaw, Poland"},{"name":"Department of Surgery, 4th Military Clinical Hospital, 50-981 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Witkiewicz","sequence":"additional","affiliation":[{"name":"Department of Oncological Surgery, Regional Specialist Hospital, 51-124 Wroclaw, Poland"},{"name":"Research and Development Centre at Regional Specialist Hospital, 51-124 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2753-8092","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Krzystek-Korpacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","unstructured":"(2024, November 10). American Cancer Society: Cancer Facts and Figures 2024, Available online: https:\/\/www.cancer.gov\/types\/colorectal."},{"key":"ref_2","unstructured":"(2024, November 10). Global Cancer Observatory (GCO). Available online: https:\/\/gco.iarc.who.int\/en."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102666","DOI":"10.1016\/j.arr.2025.102666","article-title":"Evolving landscape of colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990\u20132050)","volume":"104","author":"Zhou","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, J., Ou, D., Xie, A., Chen, D., and Li, X. (2024). Global burden and cross-country health inequalities of early-onset colorectal cancer and its risk factors from 1990 to 2021 and its projection until 2036. BMC Public Health, 24.","DOI":"10.1186\/s12889-024-20624-4"},{"key":"ref_5","first-page":"233","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.annonc.2023.12.003","article-title":"European cancer mortality predictions for the year 2024 with focus on colorectal cancer","volume":"35","author":"Santucci","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.5603\/njo.99065","article-title":"Cancer incidence and mortality in Poland in 2023","volume":"74","author":"Didkowska","year":"2024","journal-title":"Nowotw. J. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Luo, S., Gong, J., Zhu, Y., Wang, L., and Zhang, K. (2025). Global, regional, and national burden of colorectal cancer in the elderly (aged\u2009 >\u2009 60 years): A comprehensive analysis across 204 countries and territories (1990\u20132021). BMC Gastroenterol., 25.","DOI":"10.1186\/s12876-025-04184-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.puhe.2024.12.011","article-title":"Global, regional, and national burden of early-onset colorectal cancer and projection to 2050: An analysis based on the Global Burden of Disease Study 2021","volume":"238","author":"Li","year":"2025","journal-title":"Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1470-2045(24)00600-4","article-title":"Colorectal cancer incidence trends in younger versus older adults: An analysis of population-based cancer registry data","volume":"26","author":"Sung","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.soc.2017.11.010","article-title":"Surgical Treatment of Metastatic Colorectal Cancer","volume":"27","author":"Chakedis","year":"2018","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1159\/000456085","article-title":"Introduction of robotic surgery into a community hospital setting: A prospective comparison of robotic and open colorectal resection for cancer","volume":"34","author":"Zawadzki","year":"2017","journal-title":"Dig. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s40520-024-02833-4","article-title":"Robot-assisted vs. laparoscopic right hemicolectomy in octogenarians and nonagenarians: An analysis of the US nationwide inpatient sample 2005\u20132018","volume":"36","author":"Lu","year":"2024","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_14","first-page":"205","article-title":"Comparison of robotic vs laparoscopic left-sided colorectal cancer resections","volume":"17","author":"Hettiarachchi","year":"2023","journal-title":"J. Robot. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1007\/s00384-021-03966-y","article-title":"Robotic versus laparoscopic right colectomy for colon cancer: A nationwide cohort study","volume":"36","author":"Dohrn","year":"2021","journal-title":"Int. J. Color. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1245\/s10434-009-0435-3","article-title":"Robotic versus laparoscopic low anterior resection of rectal cancer: Short-term outcome of a prospective comparative study","volume":"16","author":"Baik","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, Y.T., Huang, C.W., Ma, C.J., Tsai, H.L., Yeh, Y.S., Su, W.C., Chai, C.Y., and Wang, J.Y. (2020). An observational study of patho-oncological outcomes of various surgical methods in total mesorectal excision for rectal cancer: A single center analysis. BMC Surg., 20.","DOI":"10.1186\/s12893-020-0687-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8196","DOI":"10.1007\/s00464-023-10383-5","article-title":"Uptake of robot-assisted colon cancer surgery in the Netherlands","volume":"37","author":"Sterk","year":"2023","journal-title":"Surg. Endosc."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Butnari, V., Sultana, M., Mansuri, A., Rao, C., Kaul, S., Boulton, R., Huang, J., and Rajendran, N. (2024). Comparison of early surgical outcomes of robotic and laparoscopic colorectal cancer resection reported by a busy district general hospital in England. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57110-1"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lin, C.-Y., Liu, Y.-C., Chen, C.-C., Chen, M.-C., Chiu, T.-Y., Huang, Y.-L., Chiang, S.-W., Lin, C.-L., Chen, Y.-J., and Lin, C.-Y. (2025). Robotic-Assisted Colon Cancer Surgery: Faster Recovery and Less Pain Compared to Laparoscopy in a Retrospective Propensity-Matched Study. Cancers, 17.","DOI":"10.3390\/cancers17020243"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s11701-024-01862-5","article-title":"Robotic versus laparoscopic right hemicolectomy: A systematic review of the evidence","volume":"18","author":"Meyer","year":"2024","journal-title":"J. Robot. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s00384-024-04733-5","article-title":"Impact of robotic surgery on postoperative gastrointestinal dysfunction following minimally invasive colorectal surgery: Incidence, risk factors, and short-term outcomes","volume":"39","author":"Zhang","year":"2024","journal-title":"Int. J. Color. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1007\/s00464-016-5289-8","article-title":"Comparison of short-term and oncologic outcomes of robotic and laparoscopic resection for mid- and distal rectal cancer","volume":"31","author":"Law","year":"2017","journal-title":"Surg. Endosc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Laks, S., Goldenshluger, M., Lebedeyev, A., Anderson, Y., Gruper, O., and Segev, L. (2025). Robotic Rectal Cancer Surgery: Perioperative and Long-Term Oncological Outcomes of a Single-Center Analysis Compared with Laparoscopic and Open Approach. Cancers, 17.","DOI":"10.3390\/cancers17050859"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ferrari, D., Violante, T., Novelli, M., Sassun, R., Sileo, A., and Larson, D.W. (2025). Robotic Surgery in Emergency Colorectal Procedures: Analysis of Outcomes and Future Trends. J. Am. Coll. Surg., online ahead of print.","DOI":"10.1097\/XCS.0000000000001500"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Safiejko, K., Tarkowski, R., Koselak, M., Juchimiuk, M., Tarasik, A., Pruc, M., Smereka, J., and Szarpak, L. (2022). Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients. Cancers, 14.","DOI":"10.3390\/cancers14010180"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1007\/s00268-018-04896-7","article-title":"Robotic versus conventional laparoscopic surgery for colorectal cancer: A systematic review and meta-analysis with trial sequential analysis","volume":"43","author":"Ng","year":"2019","journal-title":"World J. Surg."},{"key":"ref_28","first-page":"e37337","article-title":"A Review of robotic surgery in colorectal surgery","volume":"15","author":"Ravendran","year":"2023","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1007\/s00464-025-12065-w","article-title":"The rise of robotics: Surgical approaches for rectal cancer over time","volume":"39","author":"Simon","year":"2025","journal-title":"Surg. Endosc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, W., Liu, J., Wang, J., Huang, J., and Wang, J. (2025). Comparing robot-assisted vs. laparoscopic proctectomy for rectal cancer surgical and oncological outcomes. Front. Surg., 12.","DOI":"10.3389\/fsurg.2025.1628649"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1007\/s00464-021-08579-8","article-title":"Is newer always better? Comparing cost and short-term outcomes between laparoscopic and robotic right hemicolectomy","volume":"36","author":"Hopkins","year":"2022","journal-title":"Surg. Endosc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.asjsur.2022.06.079","article-title":"Comparison of robotic reduced-port and laparoscopic approaches for left-sided colorectal cancer surgery","volume":"46","author":"Wei","year":"2023","journal-title":"Asian J. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dobson, G.P. (2015). Addressing the Global Burden of Trauma in Major Surgery. Front. Surg., 2.","DOI":"10.3389\/fsurg.2015.00043"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/anae.15896","article-title":"Postoperative systemic inflammatory dysregulation and corticosteroids: A narrative review","volume":"78","author":"Bain","year":"2023","journal-title":"Anaesthesia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/sur.2015.184","article-title":"Persistent Inflammation, Immunosuppression, and Catabolism: Evolution of Multiple Organ Dysfunction","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Surg. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/TA.0b013e318256e000","article-title":"Persistent inflammation and immunosuppression: A common syndrome and new horizon for surgical intensive care","volume":"72","author":"Gentile","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0039-6060(96)80118-8","article-title":"Surgical stress induces a shift in the type-1\/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma","volume":"119","author":"Decker","year":"1996","journal-title":"Surgery"},{"key":"ref_38","first-page":"2135","article-title":"Cytokine expression in colon carcinoma","volume":"25","author":"Baier","year":"2005","journal-title":"Anticancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bjae.2020.04.006","article-title":"Anaesthesia, analgesia, and the surgical stress response","volume":"20","author":"Cusack","year":"2020","journal-title":"BJA Educ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1136\/gutjnl-2011-300948","article-title":"Less stress, more success? Oncological implications of surgery-induced oxidative stress","volume":"62","author":"Wang","year":"2013","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1213\/ANE.0000000000004455","article-title":"Perioperative oxidative stress: The unseen enemy","volume":"129","author":"Stevens","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1470-2045(03)01282-8","article-title":"Excisional surgery for cancer cure: Therapy at a cost","volume":"4","author":"Coffey","year":"2003","journal-title":"Lancet Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10151-014-1263-4","article-title":"Surgical stress response after colorectal resection: A comparison of robotic, laparoscopic, and open surgery","volume":"19","author":"Shibata","year":"2015","journal-title":"Tech. Coloproctol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Krzystek-Korpacka, M., Zawadzki, M., Szufnarowski, K., Bednarz-Misa, I., Gorska, S., Witkiewicz, W., and Gamian, A. (2018). The perioperative dynamics of IL-7 following robot-assisted and open colorectal surgery. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27245-z"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fleszar, M.G., Fortuna, P., Zawadzki, M., Hodurek, P., Bednarz-Misa, I., Witkiewicz, W., and Krzystek-Korpacka, M. (2021). Sex, Type of surgery, and surgical site infections are associated with perioperative cortisol in colorectal cancer patients. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040589"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00384-016-2697-0","article-title":"Comparison of inflammatory responses following robotic and open colorectal surgery: A prospective study","volume":"32","author":"Zawadzki","year":"2017","journal-title":"Int. J. Color. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Krzystek-Korpacka, M., Zawadzki, M., Lewandowska, P., Szufnarowski, K., Bednarz-Misa, I., Jacyna, K., Witkiewicz, W., and Gamian, A. (2019). Distinct chemokine dynamics in early postoperative period after open and robotic colorectal surgery. J. Clin. Med., 8.","DOI":"10.3390\/jcm8060879"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fleszar, M.G., Fortuna, P., Zawadzki, M., Kosak, B., and Krzystek-Korpacka, M. (2020). Simultaneous LC-MS\/MS-based quantification of free 3-nitro-L-tyrosine, 3-chloro-L-tyrosine, and 3-bromo-L-tyrosine in plasma of colorectal cancer patients during early postoperative period. Molecules, 25.","DOI":"10.3390\/molecules25215158"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bednarz-Misa, I., Fleszar, M.G., Zawadzki, M., Kapturkiewicz, B., Kubiak, A., Neubauer, K., Witkiewicz, W., and Krzystek-Korpacka, M. (2020). L-Arginine\/NO pathway metabolites in colorectal cancer: Relevance as disease biomarkers and predictors of adverse clinical outcomes following surgery. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061782"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12967-018-1389-7","article-title":"Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence","volume":"16","author":"Kim","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3892\/etm.2023.12194","article-title":"Clinical treatment for persistent inflammation, immunosuppression and catabolism syndrome in patients with severe acute pancreatitis (Review)","volume":"26","author":"Zhang","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.5847\/wjem.j.1920-8642.2021.03.004","article-title":"Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study","volume":"12","author":"Yin","year":"2021","journal-title":"World J. Emerg. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3389\/fimmu.2018.00595","article-title":"Sepsis and Critical Illness Research Center Investigators. Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy","volume":"9","author":"Horiguchi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ccc.2016.12.001","article-title":"Persistent Inflammation, Immunosuppression and Catabolism Syndrome","volume":"33","author":"Mira","year":"2017","journal-title":"Crit. Care Clin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.bja.2023.11.052","article-title":"Persistent inflammation, immunosuppression, and catabolism syndrome (PICS): A review of definitions, potential therapies, and research priorities","volume":"132","author":"Chadda","year":"2024","journal-title":"Br. J. Anaesth."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102","DOI":"10.12688\/f1000research.2-102.v1","article-title":"Cancer surgery induces inflammation, immunosuppression and neo-angiogenesis, but is it influenced by analgesics?","volume":"2","author":"Forget","year":"2013","journal-title":"F1000Research"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.surg.2018.04.011","article-title":"Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery","volume":"164","author":"Efron","year":"2018","journal-title":"Surgery"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, Q. (2023). Pituitary-immune bidirectional crosstalk under systemic inflammation. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002440"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0065-2776(07)96002-2","article-title":"Regulation of interferon-gamma during innate and adaptive immune responses","volume":"96","author":"Schoenborn","year":"2007","journal-title":"Adv. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Quirant-S\u00e1nchez, B., Plans-Galv\u00e1n, O., Lucas, E., Argudo, E., Martinez-C\u00e1ceres, E.M., and Arm\u00e9star, F. (2023). HLA-DR expression on monocytes and sepsis index are useful in predicting sepsis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071836"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1158\/0008-5472.CAN-12-1993","article-title":"Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells","volume":"73","author":"Tai","year":"2013","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cyto.2019.02.001","article-title":"The role of cytokines in the regulation of NK cells in the tumor environment","volume":"117","author":"Larsen","year":"2019","journal-title":"Cytokine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10020-020-00230-x","article-title":"IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19","volume":"26","author":"Chen","year":"2020","journal-title":"Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.4049\/jimmunol.168.7.3195","article-title":"IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking","volume":"168","author":"Dufour","year":"2002","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Madhurantakam, S., Lee, Z.J., Naqvi, A., and Prasad, S. (2023). Importance of IP-10 as a biomarker of host immune response: Critical perspective as a target for biosensing. Curr. Res. Biotechnol., 5.","DOI":"10.1016\/j.crbiot.2023.100130"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.immuni.2006.03.016","article-title":"Pro- and antiinflammatory cytokine signaling: Reciprocal antagonism regulates interferon-gamma production by human natural killer cells","volume":"24","author":"Yu","year":"2006","journal-title":"Immunity"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Krzystek-Korpacka, M., Mierzcha\u0142a-Pasierb, M., Zawadzki, M., Diakowska, D., and Witkiewicz, W. (2021). Serum and erythrocyte antioxidant defense in colorectal cancer patients during early postoperative period: Potential modifiers and impact on clinical outcomes. Antioxidants, 10.","DOI":"10.3390\/antiox10070999"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.it.2017.01.006","article-title":"IL-17 Signaling: The Yin and the Yang","volume":"38","author":"Amatya","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17 and IL-17-producing cells in protection versus pathology","volume":"23","author":"Mills","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1186\/s12964-024-01668-w","article-title":"IL-17 in wound repair: Bridging acute and chronic responses","volume":"22","author":"Mu","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e20190297","DOI":"10.1084\/jem.20190297","article-title":"The role of interleukin-17 in tumor development and progression","volume":"217","author":"Zhao","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/gutjnl-2015-310016","article-title":"Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer","volume":"66","author":"Amicarella","year":"2017","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41568-021-00363-z","article-title":"Interleukins in cancer: From biology to therapy","volume":"21","author":"Briukhovetska","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"115267","DOI":"10.1016\/j.ejca.2025.115267","article-title":"The role of IL-8 in cancer development and its impact on immunotherapy resistance","volume":"218","author":"Meier","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bazzichetto, C., Milella, M., Zampiva, I., Simionato, F., Amoreo, C.A., Buglioni, S., Pacelli, C., Le Pera, L., Colombo, T., and Bria, E. (2022). Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker. Biomedicines., 10.","DOI":"10.3390\/biomedicines10102631"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3892\/ol.2021.13144","article-title":"MCP-1 targeting: Shutting off an engine for tumor development (Review)","volume":"23","author":"Wang","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s00018-019-03351-7","article-title":"Tumor angiogenesis: Causes, consequences, challenges and opportunities","volume":"77","author":"Lugano","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41392-023-01460-1","article-title":"Angiogenic signaling pathways and anti-angiogenic therapy for cancer","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_79","first-page":"186","article-title":"Surgical procedure as an inducer of tumor angiogenesis","volume":"32","author":"Kong","year":"2010","journal-title":"Exp. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Shi, Z., Yao, C., Shui, Y., Li, S., and Yan, H. (2023). Research progress on the mechanism of angiogenesis in wound repair and regeneration. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1284981"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1097\/JS9.0000000000000542","article-title":"Surgical intervention as a driver of new angiogenesis in tumors-time to consider minimally invasive surgeries?","volume":"109","author":"Selvaraj","year":"2023","journal-title":"Int. J. Surg."},{"key":"ref_82","first-page":"567","article-title":"E2F1\/SP3\/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells","volume":"53","author":"Chen","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bednarz-Misa, I., Diakowska, D., Szczuka, I., Fortuna, P., Kubiak, A., Rosi\u0144czuk, J., and Krzystek-Korpacka, M. (2020). Interleukins 4 and 13 and their receptors are differently expressed in gastrointestinal tract cancers, depending on the anatomical site and disease advancement, and improve colon cancer cell viability and motility. Cancers, 12.","DOI":"10.3390\/cancers12061463"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chen, H.M., Hung, P.Y., Chen, C.H., Yu, Y.J., Syu, M.S., and Hu, M.C. (2022). HSD3B1 expression is upregulated by interleukin 4 in HT-29 colon cancer cells via multiple signaling pathways. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113572"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.7150\/ijbs.46651","article-title":"The role of interleukins in colorectal cancer","volume":"16","author":"Li","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Song, X., Traub, B., Shi, J., and Kornmann, M. (2021). Possible roles of interleukin-4 and -13 and their receptors in gastric and colon cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020727"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s00262-017-2043-6","article-title":"IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model","volume":"66","author":"Ito","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lopez-Perez, D., Prados-Lopez, B., Galvez, J., Leon, J., and Carazo, A. (2024). Eosinophils in colorectal cancer: Emerging insights into anti-tumoral mechanisms and clinical implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116098"},{"key":"ref_89","first-page":"713","article-title":"Predictive value of IL-18 and IL-10 in the prognosis of patients with colorectal cancer","volume":"18","author":"Li","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/intimm\/dxp102","article-title":"IL-5- and eosinophil-mediated inflammation: From discovery to therapy","volume":"21","author":"Kouro","year":"2009","journal-title":"Int. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"329","DOI":"10.20344\/amp.10112","article-title":"New insights into the role of tissue eosinophils in the progression of colorectal cancer: A literature review","volume":"31","author":"Saraiva","year":"2018","journal-title":"Acta Med. Port."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"155479","DOI":"10.1016\/j.cyto.2021.155479","article-title":"G-CSF in tumors: Aggressiveness, tumor microenvironment and immune cell regulation","volume":"142","author":"Karagiannidis","year":"2021","journal-title":"Cytokine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"65","DOI":"10.21037\/dmr-20-94","article-title":"Surgical stress response and cancer outcomes: A narrative review","volume":"3","author":"Huddart","year":"2020","journal-title":"Dig. Med. Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Jin, K., Qian, C., Lin, J., and Liu, B. (2023). Cyclooxygenase-2-prostaglandin E2 pathway: A key player in tumor-associated immune cells. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1099811"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.7150\/ijms.44439","article-title":"The Role of Cyclooxygenase-2 in colorectal cancer","volume":"17","author":"Sheng","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10555-018-9752-y","article-title":"The roles of the COX2\/PGE2\/EP axis in therapeutic resistance","volume":"37","author":"Tong","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.4049\/jimmunol.0903301","article-title":"Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor","volume":"184","author":"Glasner","year":"2010","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1158\/1940-6207.CAPR-21-0572","article-title":"The COX-2-PGE2 pathway promotes tumor evasion in colorectal adenomas","volume":"15","author":"Wei","year":"2022","journal-title":"Cancer Prev. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kulesza, A., Paczek, L., and Burdzinska, A. (2023). The role of COX-2 and PGE2 in the regulation of immunomodulation and other functions of mesenchymal stromal cells. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020445"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.3748\/wjg.v29.i39.5452","article-title":"Prostaglandin F2\u03b1 synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F2\u03b1-dependent and F2\u03b1-independent mechanism","volume":"29","author":"Wang","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/ijc.22755","article-title":"Prostaglandin F(2alpha) stimulates motility and invasion in colorectal tumor cells","volume":"121","author":"Qualtrough","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_102","first-page":"223","article-title":"Th1\/Th2 Balance: The Hypothesis, its Limitations, and Implications for Health and Disease","volume":"8","author":"Kidd","year":"2003","journal-title":"Altern. Med. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Bezu, L., \u00d6ks\u00fcz, A.D., Bell, M., Buggy, D., Diaz-Cambronero, O., Enlund, M., Forget, P., Gupta, A., Hollmann, M.W., and Ionescu, D. (2024). Perioperative immunosuppressive factors during cancer surgery: An updated review. Cancers, 16.","DOI":"10.3390\/cancers16132304"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Krzystek-Korpacka, M., Fleszar, M.G., Fortuna, P., Gostomska-Pampuch, K., Lewandowski, \u0141., Piasecki, T., Kosyk, B., Szel\u0105g, A., and Trocha, M. (2021). Modulation of prostanoids profile and counter-regulation of SDF-1\u03b1\/CXCR4 and VIP\/VPAC2 expression by sitagliptin in non-diabetic rat model of hepatic ischemia-reperfusion injury. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313155"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10041\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:34:44Z","timestamp":1760762084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":104,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010041"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010041","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}