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!!!