Immune parameters of mice bearing human head and neck cancer

Abstract

A xenogeneic human head and neck squamous cell carcinoma (HNSCC) model in immunocompetent mice was evaluated for its requirement of cyclosporine for progressive tumor growth. Tumor growth and T cell functions were assessed in mice receiving cyclosporine treatment for various lengths 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 absolute levels, of splenic CD4+ and CD8+ cells, and a diminished capacity to proliferate in response to concanavalin A and to be stimulated to secrete IL-2. The HNSCC tumors contributed to the immune decline since T cell functions were more depressed in the tumor bearers than in control mice receiving only cyclosporine treatment. These results demonstrate that human HNSCC tumor xenografts can grow in mice even with limited cyclosporine treatment, and that the survival of these xenografts may, in part, be due to a tumor-induced decline in select T cell functions.

The Biology of Distant Metastases in Head and Neck Cancer

“…One potentially exciting new area for tumor surveillance in HNSCC is in the area of immunological markers. The immune suppressive effects of HNSCC are well known and are due to the production of immunosuppressive cytokines and the induction of a population of CD34+ natural suppressor cells [106]. We have demonstrated that high intratumoral CD34+ content and synthesis of high levels of granulocyte-macrophage colony-stimulating factor correlate significantly with local recurrence and distant metastasis [107].…”

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

“…(3). Such an immune escape mechanism has also been suggested for HNSCC cells and might be reflected by a low T cell infiltration of tumors or by inefficient activation and generation of HNSCC-associated antigenspecific CTL as described by several investigators (20,22,25). Restoration of antigen presentation by cytokine treatment and/or gene transfer of deficient APM component consequently renders cells sensitive to CTL-mediated lysis.…”

Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

“…Samples may be further dispersed enzymatically using trypsin, DNase, collagenase or a combination thereof [ 19 ]. The cell suspension was then placed into a rich culture medium, such as DMEM or RPMI-1640 with additional fetal bovine serum (FBS) and transferred to petri-dishes or culture flasks [ 20 , 21 , 22 ]. A combination of antibiotics and antimycotics was added to prevent bacterial or fungal overgrowth, and fibroblast overgrowth was managed through selective trypsinisation or cell scraping [ 12 ].…”