Antigen‐specific tumor vaccine efficacy in vivo against prostate cancer with low class I MHC requires competent class II MHC

Neeley, Yilin C.; McDonagh, Kevin T.; Overwijk, Willem W.; Restifo, Nicholas P.; Sanda, Martin G.

doi:10.1002/pros.10136

Cited by 10 publications

(7 citation statements)

References 27 publications

(38 reference statements)

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“…The effects of specific vaccinations are much less understood. So far, the results of the limited number of studies using well-defined experimental tumours in respect to their MHC class I status indicate that it is possible to induce effective immunity against MHC class I-deficient tumours at least with immunization protocols using cytokines or costimulatory molecules as adjuvants (17,(20)(21)(22)(23). The mechanisms underlying this immunity are not fully understood; they may include for example NK, Th cells and IFNÁ production (21,24).…”

Section: Introductionmentioning

confidence: 99%

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

Reiniš

Šímová²,

Indrová³

et al. 2007

Int J Oncol

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Abstract. Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape from T-cell mediated immune responses. In this study we have investigated the immunologic crossreactivity between murine tumour cell lines expressing human papilloma virus (HPV) 16-derived E6/E7 oncoproteins with distinct surface expression of MHC class I molecules. The aims of this study were to demonstrate whether immune responses capable of coping with MHC class I-positive tumours can also be effective against their MHC class I-deficient derivatives and whether it is possible to induce immunity against MHC class I-deficient tumours by cellular vaccines based on MHC class I-deficient tumour cell lines. Our data showed that immunization with MHC class I-deficient but not with MHC class I positive tumour cells inhibited the growth of MHC class I-deficient tumours. In vivo depletion studies revealed that the mechanisms underlying effective immune responses against MHC class I-negative tumours in animals immunized with MHC class I-deficient tumour cells involved natural killer cells. The presented findings are of particular clinical relevance in the sense of construction of vaccines directed against a broad spectrum of HPV-associated tumours.

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Section: Introductionmentioning

confidence: 99%

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

Reiniš

Šímová²,

Indrová³

et al. 2007

Int J Oncol

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“…Such presentation is central to initiate primary, cellular immune responses as well as to establish efficient, durable secondary immune responses (1,2). Although long known to mediate protective immunity to bacteria and toxins, the important roles of CD4 ϩ T cells in tumor immunity and viral clearance have also been well established (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Disruption of MHC Class II-Restricted Antigen Presentation by Vaccinia Virus

Wang

Zhou

et al. 2005

The Journal of Immunology

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Vaccinia virus (VV), currently used in humans as a live vaccine for smallpox, can interfere with host immunity via several discrete mechanisms. In this study, the effect of VV on MHC class II-mediated Ag presentation was investigated. Following VV infection, the ability of professional and nonprofessional APC to present Ag and peptides to CD4+ T cells was impaired. Viral inhibition of class II Ag presentation could be detected within 1 h, with diminished T cell responses dependent upon the duration of APC infection and virus titer. Exposure of APC to replication-deficient virus also diminished class II Ag presentation. Virus infection of APC perturbed Ag presentation by newly synthesized and recycling class II molecules, with disruptions in both exogenous and cytoplasmic Ag presentation. Virus-driven expression of an endogenous Ag, failed to restore T cell responsiveness specific for this Ag in the context of MHC class II molecules. Yet, both class II protein steady-state and cell surface expression were not altered by VV. Biochemical and functional analysis revealed that VV infection directly interfered with ligand binding to class II molecules. Together, these observations suggest that disruption of MHC class II-mediated Ag presentation may be one of multiple strategies VV has evolved to escape host immune surveillance.

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“…When CD4 + cells are stimulated and maintained, the CD8 + responses are sustained for long periods of time, improving the antitumor response, and potentially leading to the development of long-lasting immunological memory against tumor Ags. Recent studies have also shown the direct requirement for competent HLA class II pathway stimulation in the reduction of HLA class I-mediated response for an effective immunotherapy approach [ 18 , 70 , 71 ]. Furthermore, secondary stimulation following HLA class II-T cell receptor binding through costimulatory molecules is required for complete T cell stimulation.…”

Section: Hla Class II Processing In Prostate Cancer Cellsmentioning

confidence: 99%

Prostate Cancer Immunotherapy: Exploiting the HLA Class II Pathway in Vaccine Design

Doonan

Haque

2015

J Clin Cell Immunol

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Prostate cancer is the second most diagnosed cancer in men and current treatment of advanced prostate cancer is ineffective. Immunotherapy has emerged as a promising treatment option for metastatic prostate cancer but its clinical application is still in the early stages of development. In order to treat metastatic prostate tumors, new directions must be taken to improve current immunotherapeutic strategies. These include the identification of effective tumor antigens (Ags), the induction of the HLA class II pathway for Ag processing and CD4 + T cell activation, and the ability of tumor cells to act like Ag presenting cells. In this review, we suggest a model for tumor Ag selection, epitope modification and self-processing for presentation by class II proteins as a means of restoring immune activation and tumor clearance. We also outline the importance of a Gamma-IFN-inducible Lysosomal Thiol reductase (GILT) in Ag and modified peptide processing by tumor cells, generation of functional epitopes for T cell recognition, and inclusion of immune checkpoint blockers in cancer immunotherapy. Taken together, this review provides a framework for the future development of novel cancer vaccines and the improvement of existing immunotherapeutics in prostate cancer.

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Antigen‐specific tumor vaccine efficacy in vivo against prostate cancer with low class I MHC requires competent class II MHC

Cited by 10 publications

References 27 publications

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

Disruption of MHC Class II-Restricted Antigen Presentation by Vaccinia Virus

Prostate Cancer Immunotherapy: Exploiting the HLA Class II Pathway in Vaccine Design

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