{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:40:30Z","timestamp":1788928830233,"version":"build-2803163510"},"reference-count":103,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health (NIH)","award":["R37CA232209"],"award-info":[{"award-number":["R37CA232209"]}]},{"name":"National Institute of Health (NIH)","award":["CA230972"],"award-info":[{"award-number":["CA230972"]}]},{"name":"National Institute of Health (NIH)","award":["BC132245_W81XWH-14-025"],"award-info":[{"award-number":["BC132245_W81XWH-14-025"]}]},{"name":"National Institute of Health (NIH)","award":["W81XWH2210009_BC210533"],"award-info":[{"award-number":["W81XWH2210009_BC210533"]}]},{"name":"National Institute of Health (NIH)","award":["W81XWH2211069_ BC211396"],"award-info":[{"award-number":["W81XWH2211069_ BC211396"]}]},{"name":"National Institute of Health (NIH)","award":["BC240179"],"award-info":[{"award-number":["BC240179"]}]},{"name":"National Institute of Health (NIH)","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["R37CA232209"],"award-info":[{"award-number":["R37CA232209"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["CA230972"],"award-info":[{"award-number":["CA230972"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["BC132245_W81XWH-14-025"],"award-info":[{"award-number":["BC132245_W81XWH-14-025"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["W81XWH2210009_BC210533"],"award-info":[{"award-number":["W81XWH2210009_BC210533"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["W81XWH2211069_ BC211396"],"award-info":[{"award-number":["W81XWH2211069_ BC211396"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["BC240179"],"award-info":[{"award-number":["BC240179"]}]},{"name":"The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}]},{"name":"Cancer Center Support Grant","award":["R37CA232209"],"award-info":[{"award-number":["R37CA232209"]}]},{"name":"Cancer Center Support Grant","award":["CA230972"],"award-info":[{"award-number":["CA230972"]}]},{"name":"Cancer Center Support Grant","award":["BC132245_W81XWH-14-025"],"award-info":[{"award-number":["BC132245_W81XWH-14-025"]}]},{"name":"Cancer Center Support Grant","award":["W81XWH2210009_BC210533"],"award-info":[{"award-number":["W81XWH2210009_BC210533"]}]},{"name":"Cancer Center Support Grant","award":["W81XWH2211069_ BC211396"],"award-info":[{"award-number":["W81XWH2211069_ BC211396"]}]},{"name":"Cancer Center Support Grant","award":["BC240179"],"award-info":[{"award-number":["BC240179"]}]},{"name":"Cancer Center Support Grant","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Peritoneal carcinomatosis (PC) is a late-stage manifestation of abdominopelvic malignancies with poor prognosis and limited treatment options. Unique biochemical mechanisms within the peritoneal cavity play a key role in disease progression and resistance to therapy. Despite current therapies like systemic chemotherapy and cytoreductive surgery, patients frequently develop severe complications, including bowel obstruction, nutritional decline, and ascites, driving the need to address the pro-tumorigenic niche in the peritoneal cavity. The immune microenvironment in PC is marked by elevated proinflammatory mediators, such as IL-6 and IL-8, which skew the response toward innate rather than adaptive immune responses. IL-8 signaling, through its receptors CXCR1 and CXCR2, promotes neutrophil recruitment, chronic inflammation, angiogenesis, epithelial\u2013mesenchymal transition, and immune evasion, making the IL-8\/CXCR1\/CXCR2 axis a potential therapeutic target in PC. Pre-clinical models provide evidence that IL-8 or CXCR1\/CXCR2 blockade may be a valuable therapeutic strategy. IL-8 targeting agents such as monoclonal antibodies (BMS-986253) and small-molecule inhibitors (SX-682, AZD5069, navarixin) have shown efficacy in mitigating tumor growth and improving the efficacy of immune checkpoint inhibitors. Phase I and II trials have demonstrated encouraging safety profiles and preliminary efficacy when treating multiple abdominopelvic malignancies. In this review, we discuss the influence of the IL-8\/CXCR1\/CXCR2 axis within the peritoneal immune environment in PC and highlight recent work using IL-8 or CXCR1\/CXCR2 blockade as a therapeutic strategy for PC. Continued research into the peritoneal immune microenvironment and the development of targeted therapies are essential for improving the management and prognosis of PC, potentially enhancing antitumor immunity and patient outcomes.<\/jats:p>","DOI":"10.3390\/curroncol32090496","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T12:18:18Z","timestamp":1757074698000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Interleukin-8-CXCR1\/2 Axis as a Therapeutic Target in Peritoneal Carcinomatosis"],"prefix":"10.3390","volume":"32","author":[{"given":"Christopher","family":"Sherry","sequence":"first","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-7148","authenticated-orcid":false,"given":"Neda","family":"Dadgar","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0581-3528","authenticated-orcid":false,"given":"Zuqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-1226","authenticated-orcid":false,"given":"Kunhong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5463-2252","authenticated-orcid":false,"given":"Ali H.","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera S.","family":"Donnenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-3330","authenticated-orcid":false,"given":"Albert D.","family":"Donnenberg","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"},{"name":"Department of Medicine, Drexel University School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-2613","authenticated-orcid":false,"given":"David L.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3935-5316","authenticated-orcid":false,"given":"Patrick L.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1245\/s10434-023-14553-6","article-title":"Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies","volume":"31","author":"Wagner","year":"2024","journal-title":"Ann. 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