Cargando…
The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging
An increased accumulation of immune-dysfunction-associated CD4(+)Foxp3(+) regulatory T cells (T(regs)) is observed in aging oral mucosa during infection. Here we studied the function of T(regs) during oral cancer development in aging mucosa. First, we found heightened proportions of T(regs) and myel...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100664/ https://www.ncbi.nlm.nih.gov/pubmed/33968777 http://dx.doi.org/10.3389/fonc.2021.669066 |
_version_ | 1783688836669243392 |
---|---|
author | Bhaskaran, Natarajan Jayaraman, Sangeetha Quigley, Cheriese Mamileti, Prerna Ghannoum, Mahmoud Weinberg, Aaron Thuener, Jason Pan, Quintin Pandiyan, Pushpa |
author_facet | Bhaskaran, Natarajan Jayaraman, Sangeetha Quigley, Cheriese Mamileti, Prerna Ghannoum, Mahmoud Weinberg, Aaron Thuener, Jason Pan, Quintin Pandiyan, Pushpa |
author_sort | Bhaskaran, Natarajan |
collection | PubMed |
description | An increased accumulation of immune-dysfunction-associated CD4(+)Foxp3(+) regulatory T cells (T(regs)) is observed in aging oral mucosa during infection. Here we studied the function of T(regs) during oral cancer development in aging mucosa. First, we found heightened proportions of T(regs) and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues. Using the mouse 4-Nitroquinoline 1-oxide(4-NQO) oral carcinogenesis model, we found that tongues of aged mice displayed increased propensity for epithelial cell dysplasia, hyperplasia, and accelerated OSCC development, which coincided with significantly increased abundance of IL-1β, T(regs), and MDSC in tongues. Partial depletion of T(regs) reduced tumor burden. Moreover, fungal abundance and dectin-1 signaling were elevated in aged mice suggesting a potential role for dectin-1 in modulating immune environment and tumor development. Confirming this tenet, dectin-1 deficient mice showed diminished IL-1β, reduced infiltration of T(regs) and MDSC in the tongues, as well as slower progression and reduced severity of tumor burden. Taken together, these data identify an important role of dectin-1 signaling in establishing the intra-tumoral immunosuppressive milieu and promoting OSCC tumorigenesis in the context of aging. |
format | Online Article Text |
id | pubmed-8100664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81006642021-05-07 The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging Bhaskaran, Natarajan Jayaraman, Sangeetha Quigley, Cheriese Mamileti, Prerna Ghannoum, Mahmoud Weinberg, Aaron Thuener, Jason Pan, Quintin Pandiyan, Pushpa Front Oncol Oncology An increased accumulation of immune-dysfunction-associated CD4(+)Foxp3(+) regulatory T cells (T(regs)) is observed in aging oral mucosa during infection. Here we studied the function of T(regs) during oral cancer development in aging mucosa. First, we found heightened proportions of T(regs) and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues. Using the mouse 4-Nitroquinoline 1-oxide(4-NQO) oral carcinogenesis model, we found that tongues of aged mice displayed increased propensity for epithelial cell dysplasia, hyperplasia, and accelerated OSCC development, which coincided with significantly increased abundance of IL-1β, T(regs), and MDSC in tongues. Partial depletion of T(regs) reduced tumor burden. Moreover, fungal abundance and dectin-1 signaling were elevated in aged mice suggesting a potential role for dectin-1 in modulating immune environment and tumor development. Confirming this tenet, dectin-1 deficient mice showed diminished IL-1β, reduced infiltration of T(regs) and MDSC in the tongues, as well as slower progression and reduced severity of tumor burden. Taken together, these data identify an important role of dectin-1 signaling in establishing the intra-tumoral immunosuppressive milieu and promoting OSCC tumorigenesis in the context of aging. Frontiers Media S.A. 2021-04-22 /pmc/articles/PMC8100664/ /pubmed/33968777 http://dx.doi.org/10.3389/fonc.2021.669066 Text en Copyright © 2021 Bhaskaran, Jayaraman, Quigley, Mamileti, Ghannoum, Weinberg, Thuener, Pan and Pandiyan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Bhaskaran, Natarajan Jayaraman, Sangeetha Quigley, Cheriese Mamileti, Prerna Ghannoum, Mahmoud Weinberg, Aaron Thuener, Jason Pan, Quintin Pandiyan, Pushpa The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title | The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title_full | The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title_fullStr | The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title_full_unstemmed | The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title_short | The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging |
title_sort | role of dectin-1 signaling in altering tumor immune microenvironment in the context of aging |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100664/ https://www.ncbi.nlm.nih.gov/pubmed/33968777 http://dx.doi.org/10.3389/fonc.2021.669066 |
work_keys_str_mv | AT bhaskarannatarajan theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT jayaramansangeetha theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT quigleycheriese theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT mamiletiprerna theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT ghannoummahmoud theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT weinbergaaron theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT thuenerjason theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT panquintin theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT pandiyanpushpa theroleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT bhaskarannatarajan roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT jayaramansangeetha roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT quigleycheriese roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT mamiletiprerna roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT ghannoummahmoud roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT weinbergaaron roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT thuenerjason roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT panquintin roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging AT pandiyanpushpa roleofdectin1signalinginalteringtumorimmunemicroenvironmentinthecontextofaging |