Survival in human colorectal cancer correlates with expression of the T-cell costimulatory molecule OX-40 (CD134)

Background: The T-cell costimulatory molecule OX-40 (CD134) is expressed on activated CD4⁺ ("helper") T cells. Such cells have been detected in human cancers, and engagement of OX-40 improves colon cancer immunity in an animal model. Methods: Sections of primary colon cancers, normal margins, mesenteric lymph nodes, and metastases were stained for OX-40 by immunohistochemistry. Cancer registry data were reviewed. Results: High levels of OX-40 positive tumor-infiltrating lymphocytes were found in 15 of 72 primary tumors. Thirty-one cases had prominent lymphocytic infiltrates expressing OX-40 at the invasive margin of the tumor. Overall, 50% of primary tumors showed high expression of OX-40. Nearly all mesenteric lymph nodes expressed OX-40, whether tumor was present or not. Normal margins of colon did not show high levels of OX-40. High OX-40 expression in the primary tumor correlated with better survival (mean survival high OX-40, 47 months, low OX-40, 35 months, P <0.05), although this correlation was not stage-independent. Conclusions: High levels of OX-40 positive lymphocytes are present in half of primary colon cancers, and this expression in primary tumors significantly correlates with better survival. This correlation with survival and our previous preclinical research suggest a basis for an OX-40 immunotherapy trial.