Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model
Joseph Zenga, Musaddiq Awan, Anne Frei, Ellie Petrie, Guru Prasad Sharma, Aditya Shreenivas, Monica Shukla, Heather A. Himburg
Abstract
Abstract Background 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. Methods 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. Results 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). Conclusions 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.