{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:44:57Z","timestamp":1773787497154,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Appendix Cancer and Pseudomyxoma Peritonei Foundation Catalyst Research Grant Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by quantifying CD3+ and CD8+ lymphocyte densities and assessing their prognostic significance. Methods: Archival tissue samples from 95 AC patients were analyzed using immunohistochemistry to assess CD3+ and CD8+ T cell densities and their ratios. Associations between lymphocyte density and clinical, pathologic, and oncologic variables were examined using Spearman\u2019s correlation, Kruskal\u2013Wallis tests, and Cox proportional hazards analysis. Results: Tumor samples exhibited substantial immunologic heterogeneity with significant rightward skew. CD3+ and CD8+ densities were higher in low-grade tumors (p = 0.02 and p = 0.01, respectively) and low-grade histologic subtypes (p = 0.01 and p = 0.006). Lymphocyte density was inversely associated with patient age and was significantly lower in high-grade and non-mucinous tumors. The CD8+:CD3+ ratio emerged as an independent prognostic marker for progression-free survival (HR = 0.39, p = 0.004), whereas absolute CD3+ and CD8+ densities were less predictive. Conclusions: This study highlights the diverse immune microenvironment in AC, with immune infiltration patterns correlating with tumor grade and histologic subtype. The CD8+:CD3+ ratio is a potential prognostic biomarker for patient stratification, underscoring its clinical significance. Future studies should expand immune biomarker panels and explore immunomodulatory therapies for lymphocyte-rich AC subsets.<\/jats:p>","DOI":"10.3390\/cancers17030542","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:53:41Z","timestamp":1738832021000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intra-Tumoral CD8+:CD3+ Lymphocyte Density Ratio in Appendix Cancer Is a Tumor Volume- and Grade-Independent Predictor of Survival"],"prefix":"10.3390","volume":"17","author":[{"given":"Chelsea","family":"Knotts","sequence":"first","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Sherry","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rose","family":"Blodgett","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-178X","authenticated-orcid":false,"given":"Catherine","family":"Lewis","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashten","family":"Omstead","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6024-810X","authenticated-orcid":false,"given":"William","family":"LaFramboise","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-7148","authenticated-orcid":false,"given":"Neda","family":"Dadgar","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-6341","authenticated-orcid":false,"given":"Ajay","family":"Goel","sequence":"additional","affiliation":[{"name":"Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 15212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","first-page":"441","article-title":"Appendiceal cancer: A review of the literature","volume":"83","author":"Sagaert","year":"2020","journal-title":"Acta Gastroenterol. 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