Antigenic variation and macrophage infiltration of human bladder tumors xenografted into nude mice

The presence of macrophages both within and around human bladder transitional cell carcinomas xenografted into nude mice has been examined using immunocytochemical staining. Nine different xenograft lines derived from bladder tumors of eight patients were stained for F4/80, MHC II and PGP-1 labelled cells. The results revealed considerable heterogeneity both within and between tumors. All of the tumors generated some macrophage response at the tumor periphery, and this was marked in two instances, UCRU-BL-13, passage 9 and UCRU-BL-17, passage 2. In only two tumors was there substantial penetration of the tumor epithelium by macrophages, though infiltrating Ia+, F4/80+, PGP-1+ cells were sometimes seen spreading along the base of the epithelial sheets. Three of the tumors were characterized by the presence of L3T4+ T lymphocytes at the invasion front. The presence of macrophages or lymphocytes either at the invasion front or within the tumors did not correlate with the pathological grade of the tumors. PGP-1 monoclonal antibodies also stained granulocytes, which were present within the tumor mass in UCRU-BL-15, passage 2, possibly reflecting the production by the tumor of G-CSF. In addition, the PGP-1 antibodies stained some of the bladder tumors cells themselves, and, in some cases, the interstitial structures within the tumors. The significance of this staining is not yet understood. The xenografted tumors will provide a useful model to examine the constraints on tumor therapy using macrophage activating stimuli.