Abstract 4715: OX40 expression improves the prognostic value of CD8 positive lymphocyte density in colorectal carcinoma
Authors: Weixler Benjamin , Droeser Raoul A. , Sorge Roberto , Delko Tarik , Nebiker Christian A. , Iezzi Giandomenica , Spagnoli Giulio C. , Kettelhack Christoph , Holzen Urs W. von , Oertli Daniel , Terracciano Luigi , Tornillo Luigi , Sconocchia Giuseppe 
Published: May 2015

Abstract
Background: The prognostic role of the immunological microenvironment in colorectal cancer (CRC) is well known. Among immune cell types, CD8 positive T lymphocyte infiltration is an established prognostic marker clearly associated with a favorable clinical course of the disease. In contrast, there is limited information about the prognostic role of OX40 positive immune cell infiltration in CRC. However, increasing evidence suggests that OX40 positive immune cell infiltration, as a single biomarker, has a positive prognostic effect in CRC patients. To the best of our knowledge, the impact of the combination of OX40 positive immune cells and CD8 positive T lymphocytes is unknown.
Methods: A tissue microarray composed of 441 biopsies was evaluated for OX40 positive immune cells and CD8 positive T lymphocyte infiltration by immunohistochemistry. The intratumoral number of tumor infiltrating cells positive for OX40 and CD8 antigens was evaluated by 2 independent investigators achieving an optimal concordance rate of 90%. According to the frequency and staining intensity, we identified four subgroups of cell population: OX40low/CD8low, OX40high/CD8low, OX40low/CD8high and OX40high/CD8high. They were correlated with clinicopathological data, and a combined survival analysis was performed.
Results: The mean age of the patients cohort was 69.9 ±10.7 years. A total of 230 (52%) biopsies were from female and 211 (48%) from male CRC patients. Both, OX40 and CD8 positive cell infiltration had a significant, prognostic impact on the clinical outcome of the disease as individual markers (p&lt;0.0001 and p=0.007, respectively). Remarkably, the combination of OX40 and CD8 positive cell infiltration (OX40high/CD8high), significantly enhanced the overall survival of these patients (p&lt;0.0001). These results were maintained after a multivariate Cox regression analysis including T and N stages, grade, vascular invasion, tumor border configuration, microsatellite stability and CD8 and OX40 positive cell infiltration suggesting that this combination is an independent prognostic factor in CRC patients.
Conclusion: The combination OX40 and CD8 positive cell infiltration significantly enhances the overall survival compared to OX40 and CD8 positive cell infiltration alone. OX40high/CD8high positive cell infiltration is an independent, favorable, prognostic marker in CRC.
Citation Format: Benjamin Weixler, Raoul A. Droeser, Roberto Sorge, Tarik Delko, Christian A. Nebiker, Giandomenica Iezzi, Giulio C. Spagnoli, Christoph Kettelhack, Urs W. von Holzen, Daniel Oertli, Luigi Terracciano, Luigi Tornillo, Giuseppe Sconocchia. OX40 expression improves the prognostic value of CD8 positive lymphocyte density in colorectal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4715. doi:10.1158/1538-7445.AM2014-4715