肿瘤免疫功能和治疗方法

2) 病毒诱发的肿瘤抗原
◆ 病毒主要通过其DNA或RNA反转录DNA整合到宿主 细胞DNA中, 及其病毒表达蛋白, 致使细胞发生恶性转 化并表达肿瘤抗原。已发现某些编码蛋白经胞质溶胶途 径被加工处理成抗原肽，通过MHC I类分子递呈于细 胞膜表面，被T细胞所识别，激发特异性CTL反应。病 毒致癌和机体存在对病毒肿瘤抗原的免疫应答已被人工 重组的病毒抗原诱导实验性动物肿瘤而加以证实。
B细胞识别的肿瘤抗原
Tumor cell
肿瘤抗原与肿瘤关系
1.肿瘤特异性抗原 2.肿瘤相关性抗原
1.肿瘤特异性抗原
1) 化学和物理致癌因素诱发的肿瘤抗原 2) 病毒诱发的肿瘤抗原 3) 癌基因和突变型抑癌基因表达的肿瘤抗原 4) 正常静止基因表达的肿瘤抗原
1) 化学和物理致癌因素诱发的肿瘤抗原
Consequences of chromosome translocation
Translocations between chromosome 22 and chromosome 9 generate Philadephia chromosomes that synthesize bcl-abl fusion transcripts that are responsible for two types of leukemia.
◆ 由同一病毒诱发的肿瘤，不论其动物种属及组织来 源如何，均表达相同的肿瘤抗原。
Experimental induction of immunity against tumor cells induced by polyoma virus(PV)
Immune response to MCA or PV
◆ 理化致癌物主要是通过直接或间接作用于细胞染色体 DNA，激活或突变的基因所表达的编码蛋白，可以是整 合到细胞膜双层类脂中的糖蛋白，但大多数为细胞内蛋 白。它们在胞浆内经处理后成为抗原肽，由MHC I类分 子递呈于细胞膜表面，被CD8 T细胞所识别，激发特异 性CTL反应，一般难以诱导B细胞产生抗体。
Wild-type p53 is required to restrain cell growth. Its activity may be lost by deletion of both wild-type alleles or by a dominant mutation in one allele.
Activation of a growth factor receptor involves ligand binding, dimerization, and autophosphorylation, A truncated oncogenic receptor that lacks the ligandbinding region is constitutively active because it is not repressed by the Nterminal domain.
◆ 常表现出明显的个体特异性。即同一化学致癌剂或 物理致癌因素在不同宿主体内，甚至在同一宿主的不同 部位所诱发的肿瘤都具有互不相同的免疫原性。
Mice were induced to produce tumors by the injection of a chemical carcinogen (methyl-cholanthrene). Tumor cells from these mice were then injected subcutaneously into genetically identical mice. Later, the growing tumor were removed surgically. Mice challenged with the same tumor were able to reject it, but those challenged with a different tumor (induced with the same carcinogen) were not. The ability to reject the tumor could be transferred with lymphoid cells.
肿瘤免疫功能和治 疗方法
抗肿瘤免疫应答是 否存在？
20世纪20年代
Lymphocytic inflammation associated with certain tumors.
A. Medullary breast carcinoma. B. Malignant melanoma. Red arrows indicate malignant cells. Yellow arrows indicate lymphocyte-rich inflammatory infiltrates.
肿瘤抗原是细胞恶性转化过程中出现异常的蛋白和多 肽分子总称。T细胞识别的MHC递呈的肿瘤抗原肽。 T细胞识别的肿瘤抗原
Different mechanisms generate tumor-specific transplantation antigens (TSTAs) and associated transplantation antigens (TATAs)
肿瘤是一群失去正常生长调控机制、发生恶 性转化的自身细胞。肿瘤免疫学是研究肿瘤的免 疫原性、机体对肿瘤的免疫应答和抗肿瘤的效应 机制、机体的免疫功能与肿瘤发生发展的相互关 系，以及肿瘤的免疫诊断和免疫防治的科学。
◆ 肿瘤抗原
◆ 机体抗肿瘤的免疫机制
◆ 肿瘤的免疫逃逸机制
◆ 肿瘤的免疫治疗
肿瘤抗原 (Tumor Antigens)
methyl-cholanthrene (MCA) polyoma virus (PV)
3) 癌基因和突变型抑癌基因表达的肿瘤抗原
◆ 在不同致癌因素和特定条件下，原癌基因可被异常激 活，抑癌基因发生突变，由此出现的异常表达产物, 导致 正常细胞癌变，并能检测到相应的编码蛋白。现已发现人 类肿瘤中存在着癌基因或突变型抑癌基因，并检测到相应 的编码蛋白。 ◆ 这类蛋白在胞内经处理分解为不同小肽，通过MHC I 类分子递呈可作为肿瘤特异性抗原肽被T细胞所识别，激 活CTL反应。