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.
Petty
John K
JK
Department of Surgery, Section of Surgical Oncology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., L223A, Portland, OR 97201-3098, USA.
He
Ken
K
Corless
Christopher L
CL
Vetto
John T
JT
Weinberg
Andrew D
AD
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011971:Receptors, Immunologic / Q000378:metabolism*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D016019:Survival Analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D000951:Antigens, Neoplasm; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7