{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:30Z","timestamp":1785426150406,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023652","name":"University of Rijeka, Croatia","doi-asserted-by":"crossref","award":["PU 925.10.0239"],"award-info":[{"award-number":["PU 925.10.0239"]}],"id":[{"id":"10.13039\/501100023652","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PU 925.10.0239"],"award-info":[{"award-number":["PU 925.10.0239"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The incidence of colorectal cancer (CRC) in developed Western countries is constantly growing. CRC represents the third most common cancer and the second leading cancer-related cause of death worldwide. Innate and adaptive immunity play a pivotal role in the tumor response, but many of these interactions are still not well understood. Granulysin (GNLY) is an effector, cytolytic molecule, present in human cytotoxic granules of different lymphocyte subpopulations, mainly in cytotoxic T cells and NK cells. Pore-forming proteins GNLY, perforin and granzymes play a key role in cell-mediated immune responses against tumors and infections. Materials and Methods: We aimed to analyze perforin and GNLY-mediated cytotoxicity in the peripheral blood of patients with CRC by flow cytometry. Simultaneously, the cells were labeled with monoclonal antibodies against perforin, GNLY and different surface antigens (CD3, CD4, CD8 and CD56). Phenotypes of lymphocyte subpopulation and expression of perforin and GNLY were analyzed using intracellular and surface immunofluorescence. Results: Total perforin and GNLY expressions in peripheral blood mononuclear cells (PBMC) were significantly lower than in the control group. Statistically significant differences were observed in the distribution of perforin and GNLY expression in different stages of tumors classified according to Dukes\u2019, indicating that the percentage of total perforin and GNLY was significantly diminished in accordance with tumor progression. Perforin and GNLY expression were significantly reduced in NK and NKT cells, accompanied by reduced cytolytic potential in patients with CRC and a consequent reduction in their ability to eliminate tumors and infected cells. Conclusions: The determination of cytotoxic potential may provide a valuable assessment of a patient\u2019s immune status and represent a novel therapeutic target. Patients with CRC exhibit markedly impaired perforin- and GNLY-mediated cytotoxicity that correlates with disease progression. Assessment and restoration of cytolytic potential may therefore serve as indicators of immune competence and promising therapeutic strategies to improve perioperative and oncologic outcomes.<\/jats:p>","DOI":"10.3390\/medicina62040791","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:53:23Z","timestamp":1776696803000},"page":"791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perforin and Granulysin-Mediated Cytotoxicity in Colorectal Cancer Patients"],"prefix":"10.3390","volume":"62","author":[{"given":"Ludvig","family":"Letica","sequence":"first","affiliation":[{"name":"Department of Surgery, University Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Medical Faculty, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana \u0160uti\u0107","family":"Lubina","sequence":"additional","affiliation":[{"name":"Community Health Centre of Primorje-Gorski Kotar County, 51000 Rijeka, Croatia"},{"name":"Department of Family Medicine, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdrinko","family":"Brekalo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Medical Faculty, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0110ordano","family":"Ba\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Surgery, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Clinical Medicine 2, Faculty of Health Studies, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7960-6069","authenticated-orcid":false,"given":"Jelena","family":"Roganovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Children\u2019s Hospital Zagreb, 10000 Zagreb, Croatia"},{"name":"Faculty of Biotechnology and Drug Development, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-6698","authenticated-orcid":false,"given":"Ana","family":"\u0110or\u0111evi\u0107","sequence":"additional","affiliation":[{"name":"Department of Business Development, Jadran Galenski Laboratorij, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid \u0160uti\u0107","family":"Udovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Dermatovenereology, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Letica","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3232-3341","authenticated-orcid":false,"given":"Ivana","family":"Kotri","sequence":"additional","affiliation":[{"name":"University Hospital for Orthopedics and Traumatology Lovran, 51415 Lovran, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Mrakov\u010di\u0107-\u0160uti\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Immunology and Pathophysiology, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Basic Medical Sciences, Faculty of Health Studies, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2174\/18735592MTEx9NTk2y","article-title":"Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes","volume":"22","author":"Baidoun","year":"2021","journal-title":"Curr. 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