肿瘤生物治疗医学课件.pptVIP

肿瘤生物治疗;肿瘤治疗类型;强调综合治疗;肿瘤生物治疗及生物调节剂;肿瘤生物治疗主要指免疫治疗;策略;Molecularandcellularrequirementforimmuneactivation

Molecules:

MHC

costimulatorymoleculeB7

Cytokines/chemokines

Antibody

Cells:

T-cell(Th;CTL);

APC;

Bcell

;

TumorAntigen

Tumorantigen:intracellular(8-11aa)+MHC1

extracellular(larger)+MHC2

Antigencategory:

pointmutationsofoncogenesorsuppressorgenes:

rasP21,P53mut+MHC1Tcell

Chromosomalrearrangements:

CMLbcr-abl+MHC1Tcell

Adultexpressinofdevelopmentalgene:

MelanomaMAGE-1+HLA-A1Tcell

Overexpressionofadultgene:

HER-2/neu

Changeincarbohydratestructure:

;肿瘤细胞的基因修饰

细胞因子:GM-CSF增强肿瘤免疫原性

趋化因子

MHC

共刺激因子:第二信号因子;肿瘤生物治疗失败原因

肿瘤负荷大

肿瘤抗原性弱，缺乏人特异性Ag

机体免疫缺陷（先天性与获得性HIV）

毒付作用

;免疫应答;免疫应答分类;

过继免疫（LAK/TIL）影响疗效因素

T细胞：体内寿命黑瘤60天正常77-87

肿瘤靶点

抗原识别

肿瘤负荷

细胞因子/共刺激因子

宿主因素：并发症;主动特异性：;Localimmune

presenceoftumor-infiltratingTlymphocyteshasbeenshowntocorrelatewithclinicaloutcomeinvertical-growth-phasemelanomaandinbreast,prostate,renal-cell,esophageal,andcolorectalcarcinomas.

IntratumoralTCells,Recurrence,andSurvivalinEpithelial

OvarianCancer

N.Engl.J.Med.2003;348(3):203-213.

ReducedInfiltrationofTumor-associatedMacrophagesinHuman

ProstateCancer:AssociationwithCancerProgression

CancerRes.,2000;60(20):5857-5861.

PrognosticSignificanceofActivatedCD8+TCellInfiltrations

withinEsophagealCarcinomas

CancerRes.2001;61(10):3932-3936.

;

Example

CD3+tumor-infiltratingTcells(intratumoral)

inovariancarcinoma

5ys:38.0%(+)vs4.5%(-)

CD8+Tcellsinfiltratedincolorectalcancer

(a)withincancercellnests