Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis
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The Ohio State University / OhioLINK
2021
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1618413341944817 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu16184133419448172021-10-05T05:10:37Z Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis Ryan, Nathan M. Anatomy and Physiology HNSCC MIF oral cancer MDSC OSCC macrophage migration inhibitory factor Head and neck squamous cell carcinoma presents itself as a public health crisis, being the tenth most diagnosed form of cancer in the United States. Alcohol and tobacco use are among the greatest risk factors for development of oral cancer, and with their decreasing use as a result of public awareness campaigns, rates of oral cancer were on the decline. However, human papillomavirus is a more recent known cause of oral cancer and cases of virally induced oral cancer are on the rise. With surgical intervention being the primary treatment option for oral cancer, targets for immunomodulatory therapies are being actively sought. Macrophage migration inhibitory factor (MIF) is a pleiotropic, pro-inflammatory cytokine that has been linked to a worse prognosis in many cancers, including some early research that would suggest the same for oral cancer, however the role that MIF plays in the context of oral cancer remains unclear. Using a murine, orthotopic head and neck cancer model in mice sufficient or deficient for MIF, our group has begun to elucidate the function of this protein within the tumor microenvironment, with a focus on its interaction with pro-tumoral myeloid derived suppressor cells (MDSC). Interestingly, we have found that MIF deficient mice have increased tumor growth and burden compared to their wild-type counterparts. Flow cytometric analysis of immune populations within the primary tumor site revealed increased accumulations of immunosuppressive M2 macrophages and MDSC in MIF deficient mice. Suppression iiiassays further demonstrate that MDSC taken from MIF deficient mice have enhanced T cell suppressive function compared to MIF sufficient MDSCs. Mechanistically, we showthat upregulation of Pdl1, Arg1, S100a8, S100a9 and Ptgs2 as well as increased lymphocyte expression of PD-1 all play a role in mediating this immunosuppression. While MIF antagonist drugs are being actively pursued in the treatment of oral cancer, none have been met with success. MIF targeted immunomodulation remains a potentially viable cancer therapeutic, however it is clear more remains to be understood about the cellular interaction of MIF within the tumor microenvironment before these targeted therapies can be effectively employed. 2021-10-04 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1618413341944817 http://rave.ohiolink.edu/etdc/view?acc_num=osu1618413341944817 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Anatomy and Physiology HNSCC MIF oral cancer MDSC OSCC macrophage migration inhibitory factor |
| spellingShingle |
Anatomy and Physiology HNSCC MIF oral cancer MDSC OSCC macrophage migration inhibitory factor Ryan, Nathan M. Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| author |
Ryan, Nathan M. |
| author_facet |
Ryan, Nathan M. |
| author_sort |
Ryan, Nathan M. |
| title |
Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| title_short |
Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| title_full |
Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| title_fullStr |
Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| title_full_unstemmed |
Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis |
| title_sort |
macrophage migration inhibitory factor and myeloid derived suppressor cell function in oral carcinogenesis |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2021 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1618413341944817 |
| work_keys_str_mv |
AT ryannathanm macrophagemigrationinhibitoryfactorandmyeloidderivedsuppressorcellfunctioninoralcarcinogenesis |
| _version_ |
1719486778824458240 |