Catch Me, --Mechanisms of Tumor Immune Escape maker 李龙 商亮 孙健 宋春艳 郁舒靓 李丽丽 If You Can

Terrorists Tumor cell T cellsoldiers

Items Camouflage Covering or blocking of tumor antigens Surface molecules change Resistance Fas/FasL TGF-β, IL-10 Surviving Immune selection Immunodeficiency

 Camouflage( 伪装 ) 1 Covering or blocking of tumor antigens on the surface of the tumor cell1 Covering or blocking of tumor antigens on the surface of the tumor cell Tumor cell Polysaccharide

2.Surface molecule of tumor cell change Lack of class I MHC

Mechanism The disorder of Fas expression and function A sFas C The unusual expression of FasL B

The disorder of Fas expression and function Absence of FasR’s expression 1 Absence of FasR’s apoptosis function 2 Esophageal carcinoma Liver carcinoma Gastric carcinoma 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 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 counterattack

culturing the FasL tumor cells and Fas sensitive Jurkat T cells(or actived T cells) the latter apoptosise s tumor cell's FasL has the function of inducing apoptosis

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 mechanism There are some kinds of mRNA variations. Cells synthesize secretory protein(sFas) sFas prevents the apoptosis mediated by FasL and anti- Fas

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.

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 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. 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 Chang discover C Ⅱ TA gene deficient mice’s immune cell 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 Ⅱ TA gene’s transcription. 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 MHC Ⅱ molecules. 1

Allavena’s study IL-10 can reduce the expression of the surface molecules in DC such as MHC- Ⅱ,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 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. Promote Th2 cells to release IL-10 to inhibit the activation 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!!!