Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment
Toll-like receptors (TLRs) are well-known for their role in cancer development as well as in directing anti-tumor immunity. Because TLRs have also been implicated in the innate recognition of the influenza virus, it was of great interest to investigate the potential TLRs’ contribution to the reducti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1308651/full |
| _version_ | 1797293792412303360 |
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| author | Kajal H. Gupta Kajal H. Gupta Eileena F. Giurini Andrew Zloza Andrew Zloza |
| author_facet | Kajal H. Gupta Kajal H. Gupta Eileena F. Giurini Andrew Zloza Andrew Zloza |
| author_sort | Kajal H. Gupta |
| collection | DOAJ |
| description | Toll-like receptors (TLRs) are well-known for their role in cancer development as well as in directing anti-tumor immunity. Because TLRs have also been implicated in the innate recognition of the influenza virus, it was of great interest to investigate the potential TLRs’ contribution to the reduction in tumor growth following intratumoral injection of an unadjuvanted influenza vaccine and the lack of antitumor response from an adjuvanted vaccine. In our previous publication, we showed that the unadjuvanted flu vaccine modulates TLR7 expression leading to anti-tumor response in a murine model of melanoma. Here, we show that the unadjuvanted and adjuvanted flu vaccines robustly stimulate different sets of TLRs, TLR3 and TLR7, and TLR4 and TLR9, respectively. In addition, the reduction in tumor growth and improved survival from intratumoral administration of the unadjuvanted vaccine was found to be diminished in TLR7-deficient mice. Finally, we observed that both vaccines have the capacity to modulate TLR expression on both innate and adaptive immune cells. Our findings add to the mechanistic understanding of the parameters that influence tumor outcomes in unadjuvanted and adjuvanted influenza vaccines. |
| first_indexed | 2024-03-07T21:20:58Z |
| format | Article |
| id | doaj.art-7da4cd63a6284dea8f2fc2aeb596c172 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-07T21:20:58Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7da4cd63a6284dea8f2fc2aeb596c1722024-02-27T11:34:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.13086511308651Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironmentKajal H. Gupta0Kajal H. Gupta1Eileena F. Giurini2Andrew Zloza3Andrew Zloza4Division of Surgical Oncology, Department of Surgery, Rush University Medical Center, Chicago, IL, United StatesDivision of Pediatric Surgery, Department of Surgery, Rush University Medical Center, Chicago, IL, United StatesDivision of Surgical Oncology, Department of Surgery, Rush University Medical Center, Chicago, IL, United StatesDivision of Surgical Oncology, Department of Surgery, The University of Texas Medical Branch, Galveston, TX, United StatesDivision of Translational and Precision Medicine, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesToll-like receptors (TLRs) are well-known for their role in cancer development as well as in directing anti-tumor immunity. Because TLRs have also been implicated in the innate recognition of the influenza virus, it was of great interest to investigate the potential TLRs’ contribution to the reduction in tumor growth following intratumoral injection of an unadjuvanted influenza vaccine and the lack of antitumor response from an adjuvanted vaccine. In our previous publication, we showed that the unadjuvanted flu vaccine modulates TLR7 expression leading to anti-tumor response in a murine model of melanoma. Here, we show that the unadjuvanted and adjuvanted flu vaccines robustly stimulate different sets of TLRs, TLR3 and TLR7, and TLR4 and TLR9, respectively. In addition, the reduction in tumor growth and improved survival from intratumoral administration of the unadjuvanted vaccine was found to be diminished in TLR7-deficient mice. Finally, we observed that both vaccines have the capacity to modulate TLR expression on both innate and adaptive immune cells. Our findings add to the mechanistic understanding of the parameters that influence tumor outcomes in unadjuvanted and adjuvanted influenza vaccines.https://www.frontiersin.org/articles/10.3389/fonc.2024.1308651/fulltoll like receptor (TLR)innate immunityflu vaccinetumor microenvironment (TME)cancer vaccine |
| spellingShingle | Kajal H. Gupta Kajal H. Gupta Eileena F. Giurini Andrew Zloza Andrew Zloza Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment Frontiers in Oncology toll like receptor (TLR) innate immunity flu vaccine tumor microenvironment (TME) cancer vaccine |
| title | Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment |
| title_full | Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment |
| title_fullStr | Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment |
| title_full_unstemmed | Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment |
| title_short | Seasonal influenza vaccines differentially activate and modulate toll-like receptor expression within the tumor microenvironment |
| title_sort | seasonal influenza vaccines differentially activate and modulate toll like receptor expression within the tumor microenvironment |
| topic | toll like receptor (TLR) innate immunity flu vaccine tumor microenvironment (TME) cancer vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1308651/full |
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