Limits...
Importance of helper T-cell activation in dendritic cell-based anticancer immunotherapy.

Schreibelt G, Bol KF, Aarntzen EH, Gerritsen WR, Punt CJ, Figdor CG, de Vries IJ - Oncoimmunology (2013)

Bottom Line: Dendritic cell-based anticancer immunotherapy is feasible, safe and results in the induction of tumor-specific immune responses, at least in a fraction of vaccinated patients.The concomitant activation of cytotoxic and helper T cells, by loading DCs with peptides or electroporating them with the corresponding mRNAs, may further enhance vaccine-induced antitumor responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Immunology; Nijmegen Centre for Molecular Life Sciences; Radboud University Nijmegen Medical Centre; Nijmegen, the Netherlands.

ABSTRACT
Dendritic cell-based anticancer immunotherapy is feasible, safe and results in the induction of tumor-specific immune responses, at least in a fraction of vaccinated patients. The concomitant activation of cytotoxic and helper T cells, by loading DCs with peptides or electroporating them with the corresponding mRNAs, may further enhance vaccine-induced antitumor responses.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Induction of tumor antigen-specific CD4+ and CD8+ T cells by dendritic cell-based vaccines. To achieve antigen presentation to both CD4+ helper and CD8+ cytotoxic T cells, dendritic cells (DCs) can either be loaded with HLA-binding peptides or electroporated with mRNA encoding full-length tumor-associated antigens (TAAs). Upon intranodal administration, DCs migrate to the T-cell areas of lymph nodes where they present TAA-derived peptides to and activate antigen-specific CD4+ and CD8+ T lymphocytes. CD4+ T cells provide help to the CD8+ counterparts via cell-to-cell interactions and by secreting several cytokines. Both activated antigen-specific CD4+ and CD8+ T cells are involved in tumor eradication.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3716737&req=5

Figure 1: Figure 1. Induction of tumor antigen-specific CD4+ and CD8+ T cells by dendritic cell-based vaccines. To achieve antigen presentation to both CD4+ helper and CD8+ cytotoxic T cells, dendritic cells (DCs) can either be loaded with HLA-binding peptides or electroporated with mRNA encoding full-length tumor-associated antigens (TAAs). Upon intranodal administration, DCs migrate to the T-cell areas of lymph nodes where they present TAA-derived peptides to and activate antigen-specific CD4+ and CD8+ T lymphocytes. CD4+ T cells provide help to the CD8+ counterparts via cell-to-cell interactions and by secreting several cytokines. Both activated antigen-specific CD4+ and CD8+ T cells are involved in tumor eradication.

Mentions: DCs present endogenous antigens complexed with MHC Class I molecules to CD8+ cytotoxic T lymphocytes (CTLs), whereas exogenous antigens are either presented in association to MHC Class II molecules to CD4+ helper T cells or cross-presented on MHC Class I molecules to CD8+ T cells. In most clinical DC-based vaccination studies performed so far, patients have been vaccinated with mature monocyte-derived DCs loaded with synthetic MHC Class I-binding peptides to induce tumor-specific CTLs. However, convincing evidence indicates that both CTLs and helper T cells are important for the induction of strong and sustained antitumor T-cell responses (Fig. 1).3 Helper T cells not only provide growth and differentiation signals to CTL precursors, but also stimulate them by reciprocally activating antigen-presenting cells, enhance their recruitment to lymph nodes and neoplastic lesions, and even exert direct antitumor effector functions. It may therefore be important to establish protocols for the simultaneous activation of both CTLs and helper T cells against tumor-associated antigens (TAAs), rather than that of CTLs alone.


Importance of helper T-cell activation in dendritic cell-based anticancer immunotherapy.

Schreibelt G, Bol KF, Aarntzen EH, Gerritsen WR, Punt CJ, Figdor CG, de Vries IJ - Oncoimmunology (2013)

Figure 1. Induction of tumor antigen-specific CD4+ and CD8+ T cells by dendritic cell-based vaccines. To achieve antigen presentation to both CD4+ helper and CD8+ cytotoxic T cells, dendritic cells (DCs) can either be loaded with HLA-binding peptides or electroporated with mRNA encoding full-length tumor-associated antigens (TAAs). Upon intranodal administration, DCs migrate to the T-cell areas of lymph nodes where they present TAA-derived peptides to and activate antigen-specific CD4+ and CD8+ T lymphocytes. CD4+ T cells provide help to the CD8+ counterparts via cell-to-cell interactions and by secreting several cytokines. Both activated antigen-specific CD4+ and CD8+ T cells are involved in tumor eradication.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716737&req=5

Figure 1: Figure 1. Induction of tumor antigen-specific CD4+ and CD8+ T cells by dendritic cell-based vaccines. To achieve antigen presentation to both CD4+ helper and CD8+ cytotoxic T cells, dendritic cells (DCs) can either be loaded with HLA-binding peptides or electroporated with mRNA encoding full-length tumor-associated antigens (TAAs). Upon intranodal administration, DCs migrate to the T-cell areas of lymph nodes where they present TAA-derived peptides to and activate antigen-specific CD4+ and CD8+ T lymphocytes. CD4+ T cells provide help to the CD8+ counterparts via cell-to-cell interactions and by secreting several cytokines. Both activated antigen-specific CD4+ and CD8+ T cells are involved in tumor eradication.
Mentions: DCs present endogenous antigens complexed with MHC Class I molecules to CD8+ cytotoxic T lymphocytes (CTLs), whereas exogenous antigens are either presented in association to MHC Class II molecules to CD4+ helper T cells or cross-presented on MHC Class I molecules to CD8+ T cells. In most clinical DC-based vaccination studies performed so far, patients have been vaccinated with mature monocyte-derived DCs loaded with synthetic MHC Class I-binding peptides to induce tumor-specific CTLs. However, convincing evidence indicates that both CTLs and helper T cells are important for the induction of strong and sustained antitumor T-cell responses (Fig. 1).3 Helper T cells not only provide growth and differentiation signals to CTL precursors, but also stimulate them by reciprocally activating antigen-presenting cells, enhance their recruitment to lymph nodes and neoplastic lesions, and even exert direct antitumor effector functions. It may therefore be important to establish protocols for the simultaneous activation of both CTLs and helper T cells against tumor-associated antigens (TAAs), rather than that of CTLs alone.

Bottom Line: Dendritic cell-based anticancer immunotherapy is feasible, safe and results in the induction of tumor-specific immune responses, at least in a fraction of vaccinated patients.The concomitant activation of cytotoxic and helper T cells, by loading DCs with peptides or electroporating them with the corresponding mRNAs, may further enhance vaccine-induced antitumor responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Immunology; Nijmegen Centre for Molecular Life Sciences; Radboud University Nijmegen Medical Centre; Nijmegen, the Netherlands.

ABSTRACT
Dendritic cell-based anticancer immunotherapy is feasible, safe and results in the induction of tumor-specific immune responses, at least in a fraction of vaccinated patients. The concomitant activation of cytotoxic and helper T cells, by loading DCs with peptides or electroporating them with the corresponding mRNAs, may further enhance vaccine-induced antitumor responses.

No MeSH data available.


Related in: MedlinePlus