Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model.

Abstract

Despite the importance of immune response and environmental stress on head and neck cancer (HNC) outcomes, no current pre-clinical stress model includes a humanized immune system. We investigated the effects of chronic stress induced by social isolation on tumor growth and human immune response in subcutaneous HNC tumors grown in NSG-SGM3 mice engrafted with a human immune system. Tumor growth (p < 0.0001) and lung metastases (p = 0.035) were increased in socially isolated versus control animals. Chronic stress increased intra-tumoral CD4⁺ T-cell infiltrate (p = 0.005), plasma SDF-1 (p < 0.0001) expression, and led to tumor cell dedifferentiation toward a cancer stem cell phenotype (CD44⁺ /ALDH^high , p = 0.025). Chronic stress induced immunophenotypic changes, increased tumor growth, and metastasis in HNC in a murine model with a humanized immune system. This model system may provide further insight into the immunologic and oncologic impact of chronic stress on patients with HNC.