title: CD40 expression in renal cell carcinoma is associated with tumor apoptosis, CD8(+) T cell frequency and patient survival.
abstract: The co-stimulatory molecule, CD40, is expressed in renal cell carcinoma (RCC) and a variety of inflammatory diseases in the kidney. We investigated the relationship between tumor-associated CD40 expression, immune milieu of the tumor microenvironment, tumor stage and survival of patients with RCC. The expression of CD40, TUNEL and CD8 in human renal cell carcinomas was analyzed by immunohistochemistry performed on tissue samples obtained at the time of surgery. Computer-assisted quantitation of protein expression was used to analyze results in connection with patient survival and tumor stage. We show for the first time that tumor-associated CD40 expression is associated with prolonged survival in RCC patients. Tumor apoptosis (TUNEL) and CD8 immunostaining were also associated with patient survival. No relation was observed between CD40 expression and tumor stage. Our results suggest CD40 may be a prognostic biomarker indicative of prolonged RCC patient survival. Strategies that up-regulate CD40 expression in some RCC patients may thus improve survival, supporting further studies of agonistic CD40 antibodies in RCC.
authors.affiliation: Cancer and Inflammation Program, NCI, Center for Cancer Research, Frederick, MD, United States. Electronic address: weissjo@mail.nih.gov.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: Statistical Consulting, Data Management Services, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
authors.forename: W
authors.initials: W
authors.lastname: Gregory Alvord
authors.affiliation: Statistical Consulting, Data Management Services, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Quiñones
authors.affiliation: Cancer and Inflammation Program, NCI, Center for Cancer Research, Frederick, MD, United States.
authors.forename: Jimmy K
authors.initials: JK
authors.lastname: Stauffer
authors.affiliation: Cancer and Inflammation Program, NCI, Center for Cancer Research, Frederick, MD, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Wiltrout
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019013:CD40 Antigens
keywords: Apoptosis; CD40; CD8; Renal cell carcinoma; Survival