癌症研究
降钙素基因相关肽
CD8型
生物
免疫监视
头颈部鳞状细胞癌
癌症
降钙素
免疫系统
内分泌学
内科学
病理
医学
免疫学
神经肽
头颈部癌
受体
作者
Lisa A. McIlvried,Megan A. Atherton,Nicole L. Horan,Tori N. Goch,Nicole N. Scheff
标识
DOI:10.1002/adbi.202200019
摘要
Head and neck squamous cell carcinoma are highly innervated by peripheral sensory neurons. Local neurotransmitter release (e.g., calcitonin gene-related peptide (CGRP)) from sensory neurons innervating cancer is linked to tumorigenesis. CGRP-immunoreactive nerve presence comprised 9.53±1.9% of total nerve area across 11 HNSCC patients. A syngeneic tongue tumor transplant mouse model of oral cancer and a global Calca knockout mouse (CGRPKO ) are used to investigate the impact of CGRP signaling on tumor growth and the associated immune response in vivo. In tumor-bearing CGRPKO mice, there is a significant reduction in tumor size over time compared to wildtype mice using two different mouse oral cancer cell lines. Furthermore, tumor tissue from CGRPKO mice had a significant increase in tumor-infiltrating CD4+ T cells, cytotoxic CD8+ T cells, and NK1.1+ NK cells compared to wildtype. Fluorescent-activated cell sorting and real-time qPCR are used to confirm that CD4+ T cells are isolated from tumor-bearing wildtype mice containing a high expression of Ramp1 compared to sham mice. These data suggest that sensory neurotransmitter CGRP may modulate oral cancer progression via tumor immunosurveillance. Understanding the relationship between sensory neurons and cancer will aid in repurposing clinically available nervous system drugs for the treatment of cancer.
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