Limits...
Investigation of a new tumor-associated glycosylated antigen as target for dendritic cell vaccination in pancreatic cancer.

Béraud E, Collignon A, Franceschi C, Olive D, Lombardo D, Mas E - Oncoimmunology (2012)

Bottom Line: Glycoproteins, as valuable targets for dendritic cell (DC)-vaccination in cancers, remain an open question.Glycosylated structures, which are aberrantly modified during cancerisation, impact positively or negatively on glycoprotein immunogenicity.Here is presented an oncofetal glycovariant of bile-salt-dependent-lipase, expressed on human tumoral pancreas and efficiently processed by DC's, inducing T-lymphocyte activation.

View Article: PubMed Central - PubMed

Affiliation: INSERM; Marseille, France; Aix-Marseille Univ ; Centre de Recherche en Oncologie biologique et Oncopharmacologie; Marseille, France.

ABSTRACT
Glycoproteins, as valuable targets for dendritic cell (DC)-vaccination in cancers, remain an open question. Glycosylated structures, which are aberrantly modified during cancerisation, impact positively or negatively on glycoprotein immunogenicity. Here is presented an oncofetal glycovariant of bile-salt-dependent-lipase, expressed on human tumoral pancreas and efficiently processed by DC's, inducing T-lymphocyte activation.

No MeSH data available.


Related in: MedlinePlus

Figure 2. T-cell activation triggered by DC loaded with pBSDL-J28 C-terminal glycopolypeptide and exposed to CD40L (A) Proliferation of CD8+ and CD4+ T-lymphocytes. The histogram shows the proliferation of CD3+ T-lymphocytes (left panel: CD8 T-lymphocytes; right panel: CD4+ T-lymphocytes) cultured with DC’s matured with CD40L and incubated without antigen, (upper panel), with pBSDL-J28 C-terminal glycopolypeptide (Cter-J28) (middle/high panel), with defucosylated pBSDL-J28 C-terminal glycopolypeptide (Cter-Def) (middle/low panel), or with synthetic non-glycosylated pBSDL-C-terminal polypeptide (Cter-Synt) (lower panel). (B) Similar increased percent of proliferating CD4+ and CD8+ T-lymphocytes after culture with mature MoDC loaded with the pBSDL-J28 C-terminal glycopolypeptide, with defucosylated pBSDL-J28 C-terminal glycopolypeptide or with synthetic non-glycosylated pBSDL-C-terminal polypeptide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376954&req=5

Figure 2: Figure 2. T-cell activation triggered by DC loaded with pBSDL-J28 C-terminal glycopolypeptide and exposed to CD40L (A) Proliferation of CD8+ and CD4+ T-lymphocytes. The histogram shows the proliferation of CD3+ T-lymphocytes (left panel: CD8 T-lymphocytes; right panel: CD4+ T-lymphocytes) cultured with DC’s matured with CD40L and incubated without antigen, (upper panel), with pBSDL-J28 C-terminal glycopolypeptide (Cter-J28) (middle/high panel), with defucosylated pBSDL-J28 C-terminal glycopolypeptide (Cter-Def) (middle/low panel), or with synthetic non-glycosylated pBSDL-C-terminal polypeptide (Cter-Synt) (lower panel). (B) Similar increased percent of proliferating CD4+ and CD8+ T-lymphocytes after culture with mature MoDC loaded with the pBSDL-J28 C-terminal glycopolypeptide, with defucosylated pBSDL-J28 C-terminal glycopolypeptide or with synthetic non-glycosylated pBSDL-C-terminal polypeptide.

Mentions: Licensing of DC’s by CD40 ligation remains the way to induce IL-12 production and subsequent Th1 polarized response, which is one of the objectives for cancer vaccination. This proved promising in our conditions as pulsing DC’s with pBSDL-J28 C-terminal glycopolypeptide and maturation with CD40L triggered CD4 and CD8 T-cell proliferation as shown in Figure 2. Thus, DC’s could use distinct endocytosis mechanisms to simultaneously introduce pBSDL-J28 into separate intracellular compartments, which were dedicated to presentation to CD8+ or CD4+ T cells. Interestingly, it has been shown that the DC’s and macrophages use only MR-endocytosed OVA antigen for CD8+ T cell activation, whereas (macro)pinocytosed and scavenger receptor-endocytosed OVA antigen were used only for CD4+ T-cell activation.20 Moreover, DC’s pulsed with either synthetic non-glycosylated pBSDL-C-terminal polypeptide or defucosylated pBSDL-J28 C-terminal glycopolypeptide induced only weak T-cell proliferation. This reduced T cell proliferation provides evidence for the pivotal implication of the fucose in the epitope recognition. Thus, these data highlight the existence of TCR(s) for pBSDL-J28 fucosylated and O-glycosylated C-terminal domain in the T-cell repertoire.


Investigation of a new tumor-associated glycosylated antigen as target for dendritic cell vaccination in pancreatic cancer.

Béraud E, Collignon A, Franceschi C, Olive D, Lombardo D, Mas E - Oncoimmunology (2012)

Figure 2. T-cell activation triggered by DC loaded with pBSDL-J28 C-terminal glycopolypeptide and exposed to CD40L (A) Proliferation of CD8+ and CD4+ T-lymphocytes. The histogram shows the proliferation of CD3+ T-lymphocytes (left panel: CD8 T-lymphocytes; right panel: CD4+ T-lymphocytes) cultured with DC’s matured with CD40L and incubated without antigen, (upper panel), with pBSDL-J28 C-terminal glycopolypeptide (Cter-J28) (middle/high panel), with defucosylated pBSDL-J28 C-terminal glycopolypeptide (Cter-Def) (middle/low panel), or with synthetic non-glycosylated pBSDL-C-terminal polypeptide (Cter-Synt) (lower panel). (B) Similar increased percent of proliferating CD4+ and CD8+ T-lymphocytes after culture with mature MoDC loaded with the pBSDL-J28 C-terminal glycopolypeptide, with defucosylated pBSDL-J28 C-terminal glycopolypeptide or with synthetic non-glycosylated pBSDL-C-terminal polypeptide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376954&req=5

Figure 2: Figure 2. T-cell activation triggered by DC loaded with pBSDL-J28 C-terminal glycopolypeptide and exposed to CD40L (A) Proliferation of CD8+ and CD4+ T-lymphocytes. The histogram shows the proliferation of CD3+ T-lymphocytes (left panel: CD8 T-lymphocytes; right panel: CD4+ T-lymphocytes) cultured with DC’s matured with CD40L and incubated without antigen, (upper panel), with pBSDL-J28 C-terminal glycopolypeptide (Cter-J28) (middle/high panel), with defucosylated pBSDL-J28 C-terminal glycopolypeptide (Cter-Def) (middle/low panel), or with synthetic non-glycosylated pBSDL-C-terminal polypeptide (Cter-Synt) (lower panel). (B) Similar increased percent of proliferating CD4+ and CD8+ T-lymphocytes after culture with mature MoDC loaded with the pBSDL-J28 C-terminal glycopolypeptide, with defucosylated pBSDL-J28 C-terminal glycopolypeptide or with synthetic non-glycosylated pBSDL-C-terminal polypeptide.
Mentions: Licensing of DC’s by CD40 ligation remains the way to induce IL-12 production and subsequent Th1 polarized response, which is one of the objectives for cancer vaccination. This proved promising in our conditions as pulsing DC’s with pBSDL-J28 C-terminal glycopolypeptide and maturation with CD40L triggered CD4 and CD8 T-cell proliferation as shown in Figure 2. Thus, DC’s could use distinct endocytosis mechanisms to simultaneously introduce pBSDL-J28 into separate intracellular compartments, which were dedicated to presentation to CD8+ or CD4+ T cells. Interestingly, it has been shown that the DC’s and macrophages use only MR-endocytosed OVA antigen for CD8+ T cell activation, whereas (macro)pinocytosed and scavenger receptor-endocytosed OVA antigen were used only for CD4+ T-cell activation.20 Moreover, DC’s pulsed with either synthetic non-glycosylated pBSDL-C-terminal polypeptide or defucosylated pBSDL-J28 C-terminal glycopolypeptide induced only weak T-cell proliferation. This reduced T cell proliferation provides evidence for the pivotal implication of the fucose in the epitope recognition. Thus, these data highlight the existence of TCR(s) for pBSDL-J28 fucosylated and O-glycosylated C-terminal domain in the T-cell repertoire.

Bottom Line: Glycoproteins, as valuable targets for dendritic cell (DC)-vaccination in cancers, remain an open question.Glycosylated structures, which are aberrantly modified during cancerisation, impact positively or negatively on glycoprotein immunogenicity.Here is presented an oncofetal glycovariant of bile-salt-dependent-lipase, expressed on human tumoral pancreas and efficiently processed by DC's, inducing T-lymphocyte activation.

View Article: PubMed Central - PubMed

Affiliation: INSERM; Marseille, France; Aix-Marseille Univ ; Centre de Recherche en Oncologie biologique et Oncopharmacologie; Marseille, France.

ABSTRACT
Glycoproteins, as valuable targets for dendritic cell (DC)-vaccination in cancers, remain an open question. Glycosylated structures, which are aberrantly modified during cancerisation, impact positively or negatively on glycoprotein immunogenicity. Here is presented an oncofetal glycovariant of bile-salt-dependent-lipase, expressed on human tumoral pancreas and efficiently processed by DC's, inducing T-lymphocyte activation.

No MeSH data available.


Related in: MedlinePlus