Abstract 2424: CD40 expression in human solid tumors and NCI60 tumor cell lines.

Abstract

Abstract Cell-surface CD40 is a member of the tumor necrosis factor receptor superfamily (TNFRSF) expressed and functionally well characterized in immune and hematopoietic cells. However, its expression and role in human solid tumors remain to be evaluated. As a molecular target currently with the antibody-based cancer therapy, it is important to characterize expression of CD40 across a range of human solid tumors and cancer cell lines. This could help improve our understanding of biology of CD40 molecule in human cancers especially epithelial tumors, and in turn increase the odds of success of targeting CD40 pathway. Expression of CD40 in the NCI60 human tumor cell lines and common types of human solid tumors were examined by immunohistochemistry in formalin-fixed and paraffin-embedded tumor specimens. CD40, predominantly membranous signal, was constitutively expressed in 15 lines, respectively derived from carcinomas of the breast, colorectum, non-small cell lung, ovary, prostate, and renal cell, of the NCI60 tumor cell line panel, and confirmed by Western blotting and gene expression microarray data available at http://dtp.nci.nih.gov/mtweb/search.jsp. CD40 expression was largely in accordance with the mRNA expression data measured by gene expression profiling. The status of CD40 was verified in MDA-MB-231, T-47D and HCT-116 cells (CD40-positive), and MCF-7 and HT-29 cells (CD40-negative) by Western blot. Moreover, CD40 was detected in tumor cells in 17% (6/34) of breast cancer, 24% (8/34) colorectal cancer, 54% (23/43) non-small cell lung cancer, and 47% (17/36) ovarian cancer. CD40 was also spotted in infiltrating lymphocytes in the tumor stroma. The data indicate that CD40 is expressed in human solid tumors with varying expression frequencies and one quarter of cancer cell lines examined. In addition, we have established a ready-for-use immunohistochemistry assay with an antibody that specifically detects CD40 in formalin-fixed and paraffin-embedded human tumor samples. Its application holds promise to evaluate the prognostic role of CD40 in human cancers. Citation Format: Dat Nguyen, Joseph E. Tomaszewski, Stephen M. Hewitt, James H. Doroshow, Sherry X. Yang. CD40 expression in human solid tumors and NCI60 tumor cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2424. doi:10.1158/1538-7445.AM2013-2424