Poly(I:C) Treatment Prevents Skin Tumor Formation in the Preclinical HPV8 Transgenic Mouse Model

Hufbauer, Martin; Rattay, Stephanie; Hagen, Christian Munch; Quaas, Alexander; Pfister, Herbert; Hartmann, Gunther; Coch, Christoph; Akgül, Baki

doi:10.1016/j.jid.2022.12.007

Cited by 3 publications

(5 citation statements)

References 68 publications

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“…Marcuzzi et al (2014) and Hufbauer et al (2022) assessed potential vaccination strategies against β-HPV-related epithelial carcinogenesis by relying on the preclinical keratin-14 (K14)-HPV8 transgenic mouse model [ 28 , 29 ]. This model preferentially expresses all early genes (E1, E2, E4, E6, and E7) of HPV8 in the epidermis and developing hair follicles [ 21 , 30 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…Hence, a cytotoxic T cell response induced by skin tattooing of HPV E6 DNA may offer protection against HPV8-related epithelial carcinogenesis, albeit unreliably. Hufbauer et al (2022) [29] explored if innate immunity-driven in situ autovaccination against the patients' own commensal β-HPV types in the skin could induce T cell immunity against β-HPV-related epithelial carcinogenesis in high-risk groups. Tattooing polyinosinic-polycytidylic acid (poly[I:C]) prevented tumour formation in eight out of eight treated mice.…”

Section: Marcuzzi Et Al (2014) and Hufbauer Et Al (2022) Assessed Pot...mentioning

confidence: 99%

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T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

Tay,

2024

Diagnostics

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Cutaneous squamous cell carcinoma (cSCC) is an invasive malignancy that disproportionately afflicts immunosuppressed individuals. The close associations of cSCC with immunosuppression and human papillomavirus (HPV) infection beget the question of how these three entities are intertwined in carcinogenesis. By exploring the role of T cell immunity in HPV-related cSCC based on the existing literature, we found that the loss of T cell immunity in the background of β-HPV infection promotes cSCC initiation following exposure to environmental carcinogens or chronic trauma. This highlights the potential of developing T-cell centred therapeutic and preventive strategies for populations with increased cSCC risk.

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Section: Resultsmentioning

confidence: 99%

Section: Marcuzzi Et Al (2014) and Hufbauer Et Al (2022) Assessed Pot...mentioning

confidence: 99%

T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

Tay,

2024

Diagnostics

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“…Twenty µg/mouse poly(I:C) [ 36 , 37 , 38 , 39 ] (HMW) VacciGrade TM (Invivogen, San Diego, CA, USA) and 20 µg/mouse 3pRNA [ 40 , 41 ] (synthesized by AG Hartmann, University Hospital Bonn, Bonn, Germany) were formulated with in vivo-jetPEI ® (Polyplus-transfection SA, New York City, NY, USA) according to the manufacturer’s protocol at an N/P ratio of 8.…”

Section: Methodsmentioning

confidence: 99%

Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode Litomosoides sigmodontis

et al. 2023

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More than two-hundred-million people are infected with filariae worldwide. However, there is no vaccine available that confers long-lasting protection against filarial infections. Previous studies indicated that vaccination with irradiated infective L3 larvae reduces the worm load. This present study investigated whether the additional activation of cytosolic nucleic acid receptors as an adjuvant improves the efficacy of vaccination with irradiated L3 larvae of the rodent filaria Litomosoides sigmodontis with the aim of identifying novel vaccination strategies for filarial infections. Subcutaneous injection of irradiated L3 larvae in combination with poly(I:C) or 3pRNA resulted in neutrophil recruitment to the skin, accompanied by higher IP-10/CXCL10 and IFN-β RNA levels. To investigate the impact on parasite clearance, BALB/c mice received three subcutaneous injections in 2-week intervals with irradiated L3 larvae in combination with poly(I:C) or 3pRNA prior to the challenge infection. Vaccination with irradiated L3 larvae in combination with poly(I:C) or 3pRNA led to a markedly greater reduction in adult-worm counts by 73% and 57%, respectively, compared to the immunization with irradiated L3 larvae alone (45%). In conclusion, activation of nucleic acid-sensing immune receptors boosts the protective immune response against L. sigmodontis and nucleic acid-receptor agonists as vaccine adjuvants represent a promising novel strategy to improve the efficacy of vaccines against filariae and potentially other helminths.

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“…This anti-tumor effect depended on the MDA5-mediated induction of interferon-induced genes. Moreover, T-cell depletion demonstrated a predominant role for CD4+ T cells in tumor prevention [ 88 ]. While HPV8 early proteins suppress MDA5-dependent cytokine secretion in vitro [ 89 ], poly(I:C) may overcome this inhibitory effect on MDA5 in vivo.…”

Section: T-cell Mediated Approaches Against Hpv-induced Lesionsmentioning

confidence: 99%

“… Graphical illustration of an hypothetical activation of an innate immunity-driven in situ autovaccination strategy against the patient’s “own” betaHPV types to induce protective T cell-mediated immunity and to prevent cSCC development (data from [ 88 ]). …”

Section: Figurementioning

confidence: 99%

Prevention and Treatment of HPV-Induced Skin Tumors

Hasche

Akgül

2023

Cancers

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Non-melanoma skin cancer (NMSC) is the most common cancer in humans with increasing incidence. Meanwhile, a growing body of evidence has provided a link between skin infections with HPV of the genus beta (betaHPV) and the development of cutaneous squamous cell carcinomas (cSCCs). Based on this association, the development of vaccines against betaHPV has become an important research topic. This review summarizes the current advances in prophylactic and therapeutic betaHPV vaccines, including progresses made in preclinical testing and clinical trials.

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Poly(I:C) Treatment Prevents Skin Tumor Formation in the Preclinical HPV8 Transgenic Mouse Model

Cited by 3 publications

References 68 publications

T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode Litomosoides sigmodontis

Prevention and Treatment of HPV-Induced Skin Tumors

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