Catch Me,
--Mechanisms of Tumor Immune Escapemaker
李龙
商亮
孙健
宋春艳
郁舒靓
李丽丽
If You Can
TerroristsTumor cell
T cell soldiers
Items
CamouflageCovering or blocking of tumor antigens
Surface molecules change
ResistanceFas/FasL
TGF-β, IL-10
SurvivingImmune selection
Immunodeficiency
Camouflage(Camouflage(伪装伪装 ))
• 1 Covering or blocking of tumor antigens 1 Covering or blocking of tumor antigens on the surface of the tumor cellon the surface of the tumor cell
Tumor cell
Polysaccharide
2.Surface molecule of tumor cell change
Lack of
class I MHC
MechanismMechanism
The disorder of Fas
expression and
function
AA
sFas
CC
The unusual expressi
on of FasL
BB
The disorder of Fas expression and function
The disorder of Fas expression and function
Absence of FasR’s expression 1
Absence of FasR’s apoptosis function2
Esophageal carcinoma
Liver carcinoma
Gastric carcinoma
phosphatase-1
Fas and Tumor ImmunityFas and Tumor Immunity
Fas ligand expression by a variety of tumor cell lines and primary tumor isolates. Expression of Fas ligand by tumor cells has been suggested as a tumor escape mechanism, how tumor cells kill activated cytotoxic T cells and thus avoid an anti-tumor immune response.
O’Connell found colon carcinoma cells express functional FasL, thus he announced the model “Fas counterattack” in tumor immune escape.
Fas counterattackFas counterattack
normal
Tumor and activated T cells
Two major pathways for CTL: Fas-mediated and perforrin-mediated
Abnormal
Fas (CD95) belongs to the supperfamily members of tumor necrosis factor ( TNF) and nerve growth factor (NGF) receptor ,which is expressed in many kinds of cells′surface.
DEAD DOMAIN:
about 70 amino acids
in the plasma region
sFas’s sFas’s mechanismmechanism
11 22 33
There are some kinds of mRNA variations.
Cells synthesize secretory protein(sFas)
sFas prevents the apoptosis mediated by FasL and anti-Fas
sFas and sFas and leukemialeukemia
In an experience, leukemia patients' sFas level is higher than normal level.
Thus, the sfas level is stable and high in the leukemia against treatment.
FasL
Fas
TNF
活化的 CD8+ T细胞
肿瘤细胞
Fas死亡相关区
TNFR
Inactive procaspase
Actived caspase
Dead tumor cell
CTL通过 FasL-Fas作用诱导细胞凋亡
Secrete immune inhibitors
(TGF-β,IL-10)
Definition
Tumor cells can secrete a variety of inhibitors to Tumor cells can secrete a variety of inhibitors to help their escape .They areTGF-β(Transforming help their escape .They areTGF-β(Transforming Growth Factor β) ,IL-10 and VEGF(Vascular Growth Factor β) ,IL-10 and VEGF(Vascular Endothelial Growth Factor) principally. This time Endothelial Growth Factor) principally. This time we mainly introduce the principle of TGF-β. Almost we mainly introduce the principle of TGF-β. Almost TGF-β mRNA and TGF-β can be detected in all TGF-β mRNA and TGF-β can be detected in all tumor cells. tumor cells.
Tumor cells can secrete a variety of inhibitors to Tumor cells can secrete a variety of inhibitors to help their escape .They areTGF-β(Transforming help their escape .They areTGF-β(Transforming Growth Factor β) ,IL-10 and VEGF(Vascular Growth Factor β) ,IL-10 and VEGF(Vascular Endothelial Growth Factor) principally. This time Endothelial Growth Factor) principally. This time we mainly introduce the principle of TGF-β. Almost we mainly introduce the principle of TGF-β. Almost TGF-β mRNA and TGF-β can be detected in all TGF-β mRNA and TGF-β can be detected in all tumor cells. tumor cells.
TGF-βTGF-β1, TGF-β2 ,TGF-β3)
The nucleotide sequences are highly homologous.
I, II, III-type
Ⅰ.TGF-β can reduce the expression of MHC class II molecule in the tumor cell surface
Chang discover C TA gene deficient mice’s immune Ⅱcell surface defect MHC class II antigen . C II TA can control MHC class II antigen expression.
Yi zhang’s research shows that TGF-β1 can significantly inhibit C TA gene’s transcription.Ⅱ
TGF-β1 can inhibit C II TA gene transcription leading to reduce MHC class II antigen expression in tumor cells
Ⅱ.TGF-β acts on DC
No or low expression of MHCⅡ molecules.
1
No or low expression of co-stimulatory molecules
2
Allavena’s study
IL-10 can reduce the expression of the surface molecules in DC such as MHC-
,CD80,CD86Ⅱ
Inhibit the differentiation and maturation of DC
Ⅲ.TGF-β acts on T cell Inhibit the proliferation and differentiation of CTL Inhibit the proliferation and differentiation of CTL
effectively, influencing to the production of relative effectively, influencing to the production of relative CTLCTL
Promote Th2 cells to release IL-10 to inhibit the Promote Th2 cells to release IL-10 to inhibit the activation of macrophage and function of Th1 cellsactivation of macrophage and function of Th1 cells. .
Immune selection in the development of cancer: no two tumors are alike
Initiation, proliferation diversification
Microevolution, selection of immune resistance
• Immune escape and unchecked proliferation
The mechanisms of tumor cell escape is far complicated. As far as we are concerned, some mechanisms need being studied more, at the same time , a few of mechanisms have synergy(协同作用)。
The study of mechanism of tumor escape exerts some influences in tumor’s occurring and development, increasing immunity state, reversing tumor escape, etc.
Declaration
Hand IN Hand
Resisting the Carcinoma Altogether!!!