OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

Weixler, Benjamin and Cremonesi, Eleonora and Sorge, Roberto and Muraro, Manuele G. and Delko, Tarik and Nebiker, Christian A. and Daster, Silvio and Governa, Valeria and Amicarella, Francesca and Soysal, Savas D. and Kettelhack, Christoph and von Holzen, Urs W. and Eppenberger-Castori, Serenella and Spagnoli, Giulio C. and Oertli, Daniel and Iezzi, Giandomenica and Terracciano, Luigi and Tornillo, Luigi and Sconocchia, Giuseppe and Droeser, Raoul A.. (2015) OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer. Oncotarget, 6 (35). pp. 37588-37599.

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Official URL: https://edoc.unibas.ch/61933/

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BACKGROUND: OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. METHODS: OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. RESULTS: OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40(high)/CD8(high) infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40(low)/CD8(high), OX40(high)/CD8(low) or OX40(low)/CD8(low) infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40(high)/CD8(high) density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. CONCLUSIONS: OX40(high)/CD8(high) density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunotherapy (Iezzi)
UniBasel Contributors:Iezzi, Giandomenica
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1949-2553 (Electronic) 1949-2553 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Nov 2018 09:33
Deposited On:03 Nov 2018 09:33

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