Levels of murine, but not human, CXCL13 are greatly elevated in a NOD-SCID xenograft model of AIDS-associated Burkitt lymphoma (P2203)

Abstract

Abstract In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL) was created by injecting cells of the AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. The chemokine ligand for CXCR5 is CXCL13, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in tumor ascites, as measured by ELISA. As shown by immunohistochemistry, tumors were extensively infiltrated with F4/80+ histiocyte-like cells, many of which also stained positively for murine CXCL13. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL, and also confirm previous results suggesting that CXCL13 is a potential biomarker for AIDS-NHL. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the identification of other potential tumor biomarkers for AIDS-NHL.