Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin
Breast cancer continues to have a high disease burden worldwide and presents an urgent need for novel therapeutic strategies to improve outcomes. The influenza vaccine offers a unique approach to enhance the anti-tumor immune response in patients with breast cancer. Our study explores the intratumor...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/225 |
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| author | Preston Daniels Stefanie Cassoday Kajal Gupta Eileena Giurini Malia E. Leifheit Andrew Zloza Amanda L. Marzo |
| author_facet | Preston Daniels Stefanie Cassoday Kajal Gupta Eileena Giurini Malia E. Leifheit Andrew Zloza Amanda L. Marzo |
| author_sort | Preston Daniels |
| collection | DOAJ |
| description | Breast cancer continues to have a high disease burden worldwide and presents an urgent need for novel therapeutic strategies to improve outcomes. The influenza vaccine offers a unique approach to enhance the anti-tumor immune response in patients with breast cancer. Our study explores the intratumoral use of the influenza vaccine in a triple-negative 4T1 mouse model of breast cancer. We show that the influenza vaccine attenuated tumor growth using a three-dose intratumoral regimen. More importantly, prior vaccination did not alter this improved anti-tumor response. Furthermore, we characterized the effect that the influenza vaccine has on the tumor microenvironment and the underlying mechanisms of action. We established that the vaccine facilitated favorable shifts in restructuring the tumor microenvironment. Additionally, we show that the vaccine’s ability to bind sialic acid residues, which have been implicated in having oncogenic functions, emerged as a key mechanism of action. Influenza hemagglutinin demonstrated binding ability to breast cancer cells through sialic acid expression. When administered intratumorally, the influenza vaccine offers a promising therapeutic strategy for breast cancer patients by reshaping the tumor microenvironment and modestly suppressing tumor growth. Its interaction with sialic acids has implications for effective therapeutic application and future research. |
| first_indexed | 2024-03-08T15:05:51Z |
| format | Article |
| id | doaj.art-f2733bc4cd70493dabad6f57ccf09d37 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:51Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f2733bc4cd70493dabad6f57ccf09d372024-01-10T14:58:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125122510.3390/ijms25010225Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine HemagglutininPreston Daniels0Stefanie Cassoday1Kajal Gupta2Eileena Giurini3Malia E. Leifheit4Andrew Zloza5Amanda L. Marzo6Department of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Surgery, Rush University Medical Center, Chicago, IL 60612, USADepartment of Surgery, Rush University Medical Center, Chicago, IL 60612, USADepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USADepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USADepartment of Internal Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL 60612, USABreast cancer continues to have a high disease burden worldwide and presents an urgent need for novel therapeutic strategies to improve outcomes. The influenza vaccine offers a unique approach to enhance the anti-tumor immune response in patients with breast cancer. Our study explores the intratumoral use of the influenza vaccine in a triple-negative 4T1 mouse model of breast cancer. We show that the influenza vaccine attenuated tumor growth using a three-dose intratumoral regimen. More importantly, prior vaccination did not alter this improved anti-tumor response. Furthermore, we characterized the effect that the influenza vaccine has on the tumor microenvironment and the underlying mechanisms of action. We established that the vaccine facilitated favorable shifts in restructuring the tumor microenvironment. Additionally, we show that the vaccine’s ability to bind sialic acid residues, which have been implicated in having oncogenic functions, emerged as a key mechanism of action. Influenza hemagglutinin demonstrated binding ability to breast cancer cells through sialic acid expression. When administered intratumorally, the influenza vaccine offers a promising therapeutic strategy for breast cancer patients by reshaping the tumor microenvironment and modestly suppressing tumor growth. Its interaction with sialic acids has implications for effective therapeutic application and future research.https://www.mdpi.com/1422-0067/25/1/225breast cancerinfluenza vaccineimmunotherapytumor microenvironmentsialic acidhemagglutinin |
| spellingShingle | Preston Daniels Stefanie Cassoday Kajal Gupta Eileena Giurini Malia E. Leifheit Andrew Zloza Amanda L. Marzo Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin International Journal of Molecular Sciences breast cancer influenza vaccine immunotherapy tumor microenvironment sialic acid hemagglutinin |
| title | Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin |
| title_full | Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin |
| title_fullStr | Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin |
| title_full_unstemmed | Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin |
| title_short | Intratumoral Influenza Vaccine Administration Attenuates Breast Cancer Growth and Restructures the Tumor Microenvironment through Sialic Acid Binding of Vaccine Hemagglutinin |
| title_sort | intratumoral influenza vaccine administration attenuates breast cancer growth and restructures the tumor microenvironment through sialic acid binding of vaccine hemagglutinin |
| topic | breast cancer influenza vaccine immunotherapy tumor microenvironment sialic acid hemagglutinin |
| url | https://www.mdpi.com/1422-0067/25/1/225 |
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