IMMUNE PARAMETERS OF MICE BEARING HUMAN HEAD AND NECK-CANCER

A xenogeneic human head and neck squamous cell carcinoma (HNSCC) model in immunocompatent mice was evaluated for its requirement of cyclospo rine for progressive tumor growth. Tumor growth and T cell functions w ere assessed in mice receiving cyclosporine treatment for various leng ths of time. Tumor cells were injected s.c. on day 1 and cyclosporine was injected i.p. daily on days 1, 1-7, 1-14, 1-21, or for the entire 28 days of tumor growth. All mice developed tumors. These tumors were confirmed to be squamous carcinomas of human origin histologically and by positive staining for human MHC class I antigen expression. Tumors were largest in mice that received cyclosporine for days 1-21 or days 1-28. Increased tumor size was associated with increased serum levels of tumor-reactive antibodies, an increased intratumoral frequency of CD4(+) and CD8(+) cells, but a diminished production of interleukin-2 (IL-2) by the tumor infiltrate. Also correlating with increasing tumor size was splenomegaly, a decline in the frequency, but not the absolu te levels, of splenic CD4(+) and CD8(+) cells, and a diminished capaci ty to proliferate in response to concanavalin A and to be stimulated t o secrete IL-2. The HNSCC tumors contributed to the immune decline sin ce T cell functions were more depressed in the tumor bearers than in c ontrol mice receiving only cyclosporine treatment. These results demon strate that human HNSCC tumor xenografts can grow in mice even with li mited cyclosporine treatment, and that the survival of these xenograft s may, in part, be due to a tumor-induced decline in select T cell fun ctions.