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Effector T cell responses unleashed by regulatory T cell ablation exacerbate oral squamous cell carcinoma
Immune suppression by CD4(+)FOXP3(+) regulatory T (Treg) cells and tumor infiltration by CD8(+) effector T cells represent two major factors impacting response to cancer immunotherapy. Using deconvolution-based transcriptional profiling of human papilloma virus (HPV)-negative oral squamous cell carc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484691/ https://www.ncbi.nlm.nih.gov/pubmed/34622236 http://dx.doi.org/10.1016/j.xcrm.2021.100399 |
Sumario: | Immune suppression by CD4(+)FOXP3(+) regulatory T (Treg) cells and tumor infiltration by CD8(+) effector T cells represent two major factors impacting response to cancer immunotherapy. Using deconvolution-based transcriptional profiling of human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCCs) and other solid cancers, we demonstrate that the density of Treg cells does not correlate with that of CD8(+) T cells in many tumors, revealing polarized clusters enriched for either CD8(+) T cells or CD4(+) Treg and conventional T cells. In a mouse model of carcinogen-induced OSCC characterized by CD4(+) T cell enrichment, late-stage Treg cell ablation triggers increased densities of both CD4(+) and CD8(+) effector T cells within oral lesions. Notably, this intervention does not induce tumor regression but instead induces rapid emergence of invasive OSCCs via an effector T cell-dependent process. Thus, induction of a T cell-inflamed phenotype via therapeutic manipulation of Treg cells may trigger unexpected tumor-promoting effects in OSCC. |
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