Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

Bommireddy, Ramireddy; Muñoz, Luis E.; Kumari, Anita; Huang, Lei; Fan, Yijian; Monterroza, Lenore; Pack, Christopher D.; Ramachandiran, Sampath; Reddy, Shaker J C; Kim, Janet; Chen, Zhuo G.; Saba, Nabil F.; Shin, Dong M.; Selvaraj, Periasamy

doi:10.3390/vaccines8020182

Cited by 16 publications

(14 citation statements)

References 52 publications

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“…[9][10][11] TMVs containing GPI-ISMs have been shown to induce immunity in murine thymoma, 11 breast cancer, 9 12 and head and neck cancer. 13 Since these TMV vaccines contain the unique antigenic signature of each individual tumor, the platform provides an opportunity to deliver a personalized vaccine immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy

Muñoz

Huang

Bommireddy

et al. 2021

J Immunother Cancer

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BackgroundPD-L1 is one of the major immune checkpoints which limits the effectiveness of antitumor immunity. Blockade of PD-L1/PD-1 has been a major improvement in the treatment of certain cancers, however, the response rate to checkpoint blockade remains low suggesting a need for new therapies. Metformin has emerged as a potential new drug for the treatment of cancer due to its effects on PD-L1 expression, T cell responses, and the immunosuppressive environment within tumors. While the benefits of metformin in combination with checkpoint blockade have been reported in animal models, little remains known about its effect on other types of immunotherapy.MethodsVaccine immunotherapy and metformin were administered to mice inoculated with tumors to investigate the effect of metformin and TMV vaccine on tumor growth, metastasis, PD-L1 expression, immune cell infiltration, and CD8 T cell phenotype. The effect of metformin on IFN-γ induced PD-L1 expression in tumor cells was assessed by flow cytometry, western blot, and RT-qPCR.ResultsWe observed that tumors that respond to metformin and vaccine immunotherapy combination show a reduction in surface PD-L1 expression compared with tumor models that do not respond to metformin. In vitro assays showed that the effect of metformin on tumor cell PD-L1 expression was mediated in part by AMP-activated protein kinase signaling. Vaccination results in increased T cell infiltration in all tumor models, and this was not further enhanced by metformin. However, we observed an increased number of CD8 T cells expressing PD-1, Ki-67, Tim-3, and CD62L as well as increased effector cytokine production after treatment with metformin and tumor membrane vesicle vaccine.ConclusionsOur data suggest that metformin can synergize with vaccine immunotherapy to augment the antitumor response through tumor-intrinsic mechanisms and also alter the phenotype and function of CD8 T cells within the tumor, which could provide insights for its use in the clinic.

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Section: Introductionmentioning

confidence: 99%

Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy

Muñoz

Huang

Bommireddy

et al. 2021

J Immunother Cancer

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“…TMV-mediated immunotherapy has been shown to be a potential enhancer of immunosuppressants for the treatment of metastatic triple-negative breast cancer. Bommireddy et al 144 found the same effects of TMV vaccines in a mouse model of head and neck squamous cell carcinoma (HNSCC). They also found that the TMV vaccines could effectively inhibit tumor growth in MOC1 and MOC2 murine oral cancer models and cooperate with anti-PD1 to prolong the survival time of tumor-bearing mice.…”

Section: Clinical Applications Of Tmvsmentioning

confidence: 84%

Roles of Microvesicles in Tumor Progression and Clinical Applications

Zhu¹,

Li²,

Yi³

et al. 2021

IJN

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Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids can be used as biomarkers for cancer diagnosis or assessment of prognosis. Tumor-derived microvesicles can also be deployed to reverse drug resistance of tumor regenerative cells, or to deliver chemotherapeutic drugs and oncolytic adenovirus for the treatment of cancer patients. This review summarizes the general characteristics of tumor-derived microvesicles, focusing on their biological characteristics, their involvement in tumor progression, and their clinical applications.

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“…The findings suggest the prospect of a personalized therapeutic vaccine for HNSCC. The application of surgically removed tumor tissue to prepare TMV for the production of a personalized vaccine for individual patients in future clinical practice (Bommireddy et al, 2020).…”

Section: Personalized Antigen Vaccinesmentioning

confidence: 99%

Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Head and neck squamous cell carcinoma (HNSCC) have a high incidence and mortality rate, and investigating the pathogenesis and potential therapeutic strategies of HNSCC is required for further progress. Immunotherapy is a considerable therapeutic strategy for HNSCC due to its potential to produce a broad and long-lasting antitumor response. However, immune escape, which involves mechanisms including dyregulation of cytokines, perturbation of immune checkpoints, and recruitment of inhibitory cell populations, limit the efficacy of immunotherapy. Currently, multiple immunotherapy strategies for HNSCC have been exploited, including immune checkpoint inhibitors, costimulatory agonists, antigenic vaccines, oncolytic virus therapy, adoptive T cell transfer (ACT), and epidermal growth factor receptor (EGFR)-targeted therapy. Each of these strategies has unique advantages, and the appropriate application of these immunotherapies in HNSCC treatment has significant value for patients. Therefore, this review comprehensively summarizes the mechanisms of immune escape and the characteristics of different immunotherapy strategies in HNSCC to provide a foundation and consideration for the clinical treatment of HNSCC.

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Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

Cited by 16 publications

References 52 publications

Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy

Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy

Roles of Microvesicles in Tumor Progression and Clinical Applications

Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma

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