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Immunotherapy of HPV-associated head and neck cancer: Critical parameters.

Nizard M, Sandoval F, Badoual C, Pere H, Terme M, Hans S, Benhamouda N, Granier C, Brasnu D, Tartour E - Oncoimmunology (2013)

Bottom Line: Various arguments support the development of a vaccine targeting human papillomavirus (HPV) for the treatment of HPV-associated head and neck cancer.However, the mucosal localization of this tumor, the HPV-driven downregulation of MHC Class I molecules and various other immunosuppressive mechanisms must be carefully considered to improve the clinical efficacy of such an immunotherapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: INSERM U970 PARCC; Université Paris Descartes; Paris, France.

ABSTRACT
Various arguments support the development of a vaccine targeting human papillomavirus (HPV) for the treatment of HPV-associated head and neck cancer. However, the mucosal localization of this tumor, the HPV-driven downregulation of MHC Class I molecules and various other immunosuppressive mechanisms must be carefully considered to improve the clinical efficacy of such an immunotherapeutic strategy.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Critical parameters to improve the efficacy of therapeutic HPV-targeting vaccines in head and neck cancer patients. (A) The intranasal (mucosal) route of immunization significantly potentiates the efficacy of HPV-targeting vaccines. (B) As HPV proteins including E5 and E7 can downregulate MHC Class I molecules, measuring the expression of the latter on the surface of tumor cells may allow for the selection of patients who are most likely to respond to anticancer immune responses elicited by HPV-targeting vaccines. (C) Malignant cells activate various immunosuppressive mechanisms, including the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressive cells, the activation of immune checkpoints on activated T cells, etc. Hence, drugs that alleviate immunosuppression should be combined with anticancer vaccines to improve their therapeutic potential.
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Figure 1: Figure 1. Critical parameters to improve the efficacy of therapeutic HPV-targeting vaccines in head and neck cancer patients. (A) The intranasal (mucosal) route of immunization significantly potentiates the efficacy of HPV-targeting vaccines. (B) As HPV proteins including E5 and E7 can downregulate MHC Class I molecules, measuring the expression of the latter on the surface of tumor cells may allow for the selection of patients who are most likely to respond to anticancer immune responses elicited by HPV-targeting vaccines. (C) Malignant cells activate various immunosuppressive mechanisms, including the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressive cells, the activation of immune checkpoints on activated T cells, etc. Hence, drugs that alleviate immunosuppression should be combined with anticancer vaccines to improve their therapeutic potential.

Mentions: The development of HPV-targeting vaccines for the therapy of oropharyngeal tumors is a logical strategy based on to the elevated incidence of HPV+ lesions as well as on promising preclinical and clinical results. However, the anatomical localization of head and neck cancers and their highly immunosuppressive microenvironment require these vaccines to be administered via the mucosal route and to be combined with strategies that limit immunosuppression (Fig. 1). Lastly, the selection of patients whose tumors express MHC Class I molecules in spite of the presence of HPV can further enhance the clinical efficacy of this immunotherapeutic regimen.


Immunotherapy of HPV-associated head and neck cancer: Critical parameters.

Nizard M, Sandoval F, Badoual C, Pere H, Terme M, Hans S, Benhamouda N, Granier C, Brasnu D, Tartour E - Oncoimmunology (2013)

Figure 1. Critical parameters to improve the efficacy of therapeutic HPV-targeting vaccines in head and neck cancer patients. (A) The intranasal (mucosal) route of immunization significantly potentiates the efficacy of HPV-targeting vaccines. (B) As HPV proteins including E5 and E7 can downregulate MHC Class I molecules, measuring the expression of the latter on the surface of tumor cells may allow for the selection of patients who are most likely to respond to anticancer immune responses elicited by HPV-targeting vaccines. (C) Malignant cells activate various immunosuppressive mechanisms, including the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressive cells, the activation of immune checkpoints on activated T cells, etc. Hence, drugs that alleviate immunosuppression should be combined with anticancer vaccines to improve their therapeutic potential.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716751&req=5

Figure 1: Figure 1. Critical parameters to improve the efficacy of therapeutic HPV-targeting vaccines in head and neck cancer patients. (A) The intranasal (mucosal) route of immunization significantly potentiates the efficacy of HPV-targeting vaccines. (B) As HPV proteins including E5 and E7 can downregulate MHC Class I molecules, measuring the expression of the latter on the surface of tumor cells may allow for the selection of patients who are most likely to respond to anticancer immune responses elicited by HPV-targeting vaccines. (C) Malignant cells activate various immunosuppressive mechanisms, including the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressive cells, the activation of immune checkpoints on activated T cells, etc. Hence, drugs that alleviate immunosuppression should be combined with anticancer vaccines to improve their therapeutic potential.
Mentions: The development of HPV-targeting vaccines for the therapy of oropharyngeal tumors is a logical strategy based on to the elevated incidence of HPV+ lesions as well as on promising preclinical and clinical results. However, the anatomical localization of head and neck cancers and their highly immunosuppressive microenvironment require these vaccines to be administered via the mucosal route and to be combined with strategies that limit immunosuppression (Fig. 1). Lastly, the selection of patients whose tumors express MHC Class I molecules in spite of the presence of HPV can further enhance the clinical efficacy of this immunotherapeutic regimen.

Bottom Line: Various arguments support the development of a vaccine targeting human papillomavirus (HPV) for the treatment of HPV-associated head and neck cancer.However, the mucosal localization of this tumor, the HPV-driven downregulation of MHC Class I molecules and various other immunosuppressive mechanisms must be carefully considered to improve the clinical efficacy of such an immunotherapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: INSERM U970 PARCC; Université Paris Descartes; Paris, France.

ABSTRACT
Various arguments support the development of a vaccine targeting human papillomavirus (HPV) for the treatment of HPV-associated head and neck cancer. However, the mucosal localization of this tumor, the HPV-driven downregulation of MHC Class I molecules and various other immunosuppressive mechanisms must be carefully considered to improve the clinical efficacy of such an immunotherapeutic strategy.

No MeSH data available.


Related in: MedlinePlus