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Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model. Head Neck 2022 06;44(6):1324-1334

Date

03/10/2022

Pubmed ID

35261119

Pubmed Central ID

PMC9081149

DOI

10.1002/hed.27028

Scopus ID

2-s2.0-85125920861

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 (pA <a??0.0001) and lung metastases (pA =a??0.035) were increased in socially isolated versus control animals. Chronic stress increased intra-tumoral CD4+ T-cell infiltrate (pA =a??0.005), plasma SDF-1 (pA <a??0.0001) expression, and led to tumor cell dedifferentiation toward a cancer stem cell phenotype (CD44+ /ALDHhigh , pA =a??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.

Author List

Zenga J, Awan MJ, Frei A, Petrie E, Sharma GP, Shreenivas A, Shukla M, Himburg HA

Authors

Musaddiq J. Awan MD Assistant Professor in the Radiation Oncology department at Medical College of Wisconsin
Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin
Aditya Shreenivas MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Monica E. Shukla MD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin
Joseph Zenga MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin