Transcript 05070302

Catch Me,
If You Can
--Mechanisms of Tumor Immune Escape
宋春艳
李龙
商亮
孙健
maker
郁舒靓
李丽丽
Tumor cell
Terrorists
T cell
soldiers
Items
Camouflage
Resistance
Surviving
Covering or blocking of tumor antigens
Surface molecules change
Fas/FasL
TGF-β, IL-10
Immune selection
Immunodeficiency
Camouflage(伪装)
• 1 Covering or blocking of tumor antigens on
the surface of the tumor cell
Polysaccharide
Tumor cell
2.Surface molecule of tumor cell change
Lack of
class I MHC
Mechanism
A
The
disorder of
Fas
expression
and
function
B
The
unusual
expression
of FasL
C
sFas
The disorder of Fas expression and function
1
Absence of FasR’s expression
Esophageal carcinoma
Liver carcinoma
Gastric carcinoma
2
Absence of FasR’s apoptosis function
phosphatase-1
Fas 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 antitumor immune response.
O’Connell found colon carcinoma
cells express functional FasL, thus he
announced the model “Fas
counterattack” in tumor immune
escape.
Fas counterattack
the latter
apoptosise
s
culturing the FasL
tumor cells and Fas
sensitive Jurkat T
cells(or actived T cells)
tumor cell's FasL
has the function of
inducing apoptosis
53
52
51
50
Fas
Tcell/T
cell
49
48
47
Peripheral Primary
blood
tumor
normal
Abnormal
Tumor and activated T cells
Two major pathways for CTL: Fas-mediated and perforrin-mediated
Key words to Fas
DEAD
DOMAIN:
about 70 amino
acids in the
plasma region
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.
sFas’s mechanism
1
There are
some kinds of
mRNA
variations.
2
Cells
synthesize
secretory
protein(sFas)
3
sFas prevents
the apoptosis
mediated by
FasL and antiFas
sFas and leukemia
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.
活化的CD8+ T细胞
Fas死亡相关区
FasL
TNF
Fas
TNFR
肿瘤细胞
Inactive
procaspase
Actived
caspase
CTL通过FasL-Fas作用诱导细胞凋亡
Dead
tumor
cell
Secrete immune inhibitors
(TGF-β,IL-10)
Definition
Tumor cells can secrete a variety of inhibitors to help
their escape .They areTGF-β(Transforming Growth
Factor β) ,IL-10 and VEGF(Vascular Endothelial
Growth Factor) principally. This time we mainly
introduce the principle of TGF-β. Almost TGF-β mRNA
and TGF-β can be detected in all tumor cells.
TGF-β
TGF-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
Yi zhang’s research shows that TGF-β1 can
significantly inhibit CⅡTA gene’s transcription.
Chang discover CⅡTA gene deficient mice’s immune
cell surface defect MHC class II antigen . C II TA can
control MHC class II antigen expression.
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.
No or low expression of co-stimulatory molecules
1
2
Allavena’s study
IL-10 can reduce the expression of the
surface molecules in DC such as MHCⅡ,CD80,CD86
Inhibit the differentiation
and maturation of DC
Ⅲ.TGF-β acts on T cell
 Inhibit the proliferation and differentiation of CTL
effectively, influencing to the production of relative
CTL
 Promote Th2 cells to release IL-10 to inhibit the
activation of macrophage and function of Th1 cells.
IL-10
Th2
Immune selection
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!!!