Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

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Abstract

While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4+ cell populations and their production of select cytokines that occur in mice with carcinogen-induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17-type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF-β type 1 receptor inhibitor plus IL-23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer.

What's new?

While premalignant oral lesions generally are small and localized, their immunological impact on distant tissues is unknown. Here, the spleens and regional lymph nodes of mice with carcinogen-induced premalignant oral lesions were found to trend toward Th1- and Th17-type phenotypes. As lesions advanced to oral cancer, phenotypes transitioned to Treg and TGF-β production. In mice with premalignant lesions, Th17 was sustained following treatment with a TGF-β type 1 receptor inhibitor and IL-23. Treatment also elevated the production of other immunological mediators by the spleen and regional lymph nodes and decreased the rate of progression of premalignant oral lesions.

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