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 (Tregs) is observed in aging oral mucosa during infection. Here we studied the function of Tregs during oral cancer development in aging mucosa. First, we found heightened proportions of Tregs and myeloid-derive...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.669066/full |
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| author | Natarajan Bhaskaran Sangeetha Jayaraman Cheriese Quigley Prerna Mamileti Mahmoud Ghannoum Mahmoud Ghannoum Aaron Weinberg Aaron Weinberg Jason Thuener Quintin Pan Quintin Pan Pushpa Pandiyan Pushpa Pandiyan Pushpa Pandiyan |
| author_facet | Natarajan Bhaskaran Sangeetha Jayaraman Cheriese Quigley Prerna Mamileti Mahmoud Ghannoum Mahmoud Ghannoum Aaron Weinberg Aaron Weinberg Jason Thuener Quintin Pan Quintin Pan Pushpa Pandiyan Pushpa Pandiyan Pushpa Pandiyan |
| author_sort | Natarajan Bhaskaran |
| collection | DOAJ |
| description | An increased accumulation of immune-dysfunction-associated CD4+Foxp3+ regulatory T cells (Tregs) is observed in aging oral mucosa during infection. Here we studied the function of Tregs during oral cancer development in aging mucosa. First, we found heightened proportions of Tregs 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, Tregs, and MDSC in tongues. Partial depletion of Tregs 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 Tregs 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. |
| first_indexed | 2024-12-23T23:29:50Z |
| format | Article |
| id | doaj.art-eda5ba238167456c96e6558351a54fb2 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-23T23:29:50Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-eda5ba238167456c96e6558351a54fb22022-12-21T17:26:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.669066669066The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of AgingNatarajan Bhaskaran0Sangeetha Jayaraman1Cheriese Quigley2Prerna Mamileti3Mahmoud Ghannoum4Mahmoud Ghannoum5Aaron Weinberg6Aaron Weinberg7Jason Thuener8Quintin Pan9Quintin Pan10Pushpa Pandiyan11Pushpa Pandiyan12Pushpa Pandiyan13Department of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDermatology, School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesCase Comprehensive Cancer Center, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesOtolaryngology-Head and Neck surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesOtolaryngology-Head and Neck surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Biological Sciences, School of Dental Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesCase Comprehensive Cancer Center, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesAn increased accumulation of immune-dysfunction-associated CD4+Foxp3+ regulatory T cells (Tregs) is observed in aging oral mucosa during infection. Here we studied the function of Tregs during oral cancer development in aging mucosa. First, we found heightened proportions of Tregs 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, Tregs, and MDSC in tongues. Partial depletion of Tregs 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 Tregs 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.669066/fullTregFoxp3Treg17IL-1βCandidaoral cancer |
| spellingShingle | Natarajan Bhaskaran Sangeetha Jayaraman Cheriese Quigley Prerna Mamileti Mahmoud Ghannoum Mahmoud Ghannoum Aaron Weinberg Aaron Weinberg Jason Thuener Quintin Pan Quintin Pan Pushpa Pandiyan Pushpa Pandiyan Pushpa Pandiyan The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging Frontiers in Oncology Treg Foxp3 Treg17 IL-1β Candida oral cancer |
| 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 | Treg Foxp3 Treg17 IL-1β Candida oral cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.669066/full |
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