ACCELERATED-GROWTH OF MELANOMAS AFTER SPECIFIC IMMUNE DESTRUCTION OF TUMOR STROMA IN A MOUSE MODEL

Destruction of the entire stroma in a tumor could provide a stringent test of the prospects for tumor eradication in a single treatment, Thi s possibility was investigated by experimental immune destruction of t he stroma in a mouse melanoma model, Melanomas were first produced by grafting skin from transgenic C57BL/6 females of high-melanoma suscept ibility to low-susceptibility transgenic males so that the malignant c ells would be genetically female and the stromal cells genetically mal e, Subcutaneous transplant lines were then established from the melano tic and the amelanotic zones of such a melanoma and were carried in tr ansgenic male hosts to ensure the male composition of the stroma. Thus , the male-specific H-Y histocompatibility antigen, which is ubiquitou sly expressed on male cells, could provide the target for an immune at tack against the stroma. The transplant lines were next passaged once in transgenic females preimmunized against the H-Y antigen by having r eceived and rejected a graft of C57BL/6 nontransgenic male skin. The a ntistromal immune response of these hosts did not prevent recovery of the tumors, which required a substantially prolonged latency. However, after retransplantation to nonimmunized males and females, the latenc y was markedly shortened from the original level. Thus, the treatment had indirectly selected for more rapidly growing tumor cells and haste ned malignant progression.