Analysis of the mechanism of defective autologous mixed lymphocyte reaction in cancer patients

癌症患者自体混合淋巴细胞反应缺陷的机制分析

• 批准号: 03670596
• 负责人: YAMAUE Hiroki
• 金额: $ 1.41万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670596/
• 关键词: Autologous mixed lymphocyte reaction; Gastric carcinoma; Autoreactive T cell; HLA-DR antigen; AMLR-killer; Autologous tumor-killing activity; Immune Surveillance; AMLR-killer; CD4、CD8; ヘルパーT細胞; Interleukin-2; Interleukin-2 receptor; 脾臓; 免疫監視機

The AMLR in cancer patients was suppressed compared with that in controls, and its suppression was observed even in early-stage patients. The expression of HLA-DR antigen on non-T cells was suppressed in cancer patients. Neither CD4+ nor CD8+ cells sorted from T cells of cancer patients had enough response to auto-non-T cells. The proliferative response of autoreactive T cell clone from the spleen of a cancer patient was also suppressed. It is suggested that these disturbances cause the suppression of the AMLR in cancer patients.The non-specific or autologous tumor-specific cytotoxic activity was generated in the AMLR.This cytotoxic activity was impaired in cancer patients, and related with AMLR activity. The major population of AMLR-killer cells recognizing autologous tumor cells was CD4+. Autoreactive CD4+ T cell clones had cytotoxic activity against auto-PHA blasts, but not allo-PHA blasts. It is suggested that autoreactive T cell clones have autotumor-killing activity.Thus, the mechanism of self-recognition represented by AMLR might play a very important role in immunological surveillance in cancer patients, which was proved by clinical course of postoperative patients.

与对照组相比，癌症患者的 AMLR 受到抑制，甚至在早期患者中也观察到其抑制。癌症患者的非 T 细胞上 HLA-DR 抗原的表达受到抑制。从癌症患者的 T 细胞中分选的 CD4+ 和 CD8+ 细胞都没有对自身非 T 细胞产生足够的反应。来自癌症患者脾脏的自身反应性 T 细胞克隆的增殖反应也受到抑制。提示这些干扰导致癌症患者中AMLR的抑制。AMLR中产生非特异性或自体肿瘤特异性细胞毒活性。这种细胞毒活性在癌症患者中受损，并且与AMLR活性相关。识别自体肿瘤细胞的 AMLR 杀伤细胞的主要群体是 CD4+。自身反应性 CD4+ T 细胞克隆对自身 PHA 母细胞具有细胞毒活性，但对同种异体 PHA 母细胞没有细胞毒活性。提示自身反应性T细胞克隆具有自身杀伤肿瘤活性。因此，以AMLR为代表的自我识别机制可能在癌症患者的免疫监测中发挥非常重要的作用，这一点已被术后患者的临床病程所证明。

项目成果

Takuya Tsunoda et al.: "The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumorーinfiltrating lymphocytes from patients with malignant tumor" Biotherapy. 4. 9-15 (1992)

Takuy​​a Tsunoda 等：“白细胞介素 4 和白细胞介素 2 对恶性肿瘤患者肿瘤浸润淋巴细胞增殖的促进作用”生物治疗 4. 9-15 (1992)。

Makoto Iwahashi et al.: "An autoreactive Tcell clone generated in the autologous mixed lymphocyte reaction in a patient with gastric carcinoma" Journal of Clinical and Laboratory Immunology. (submitted). (1994)

Makoto Iwahashi 等人：“胃癌患者自体混合淋巴细胞反应中产生的自身反应性 T 细胞克隆”《临床和实验室免疫学杂志》。

Hiroki Yamaue et al.: "Chemosensitivity testing with highly purified fresh tuman tuman cells with the MTT colorimetric assay" European Journal of Cancer. 27. 1258-1263 (1991)

Hiroki Yamaue 等人：“采用 MTT 比色测定法对高度纯化的新鲜 tuman tuman 细胞进行化学敏感性测试”《欧洲癌症杂志》。

Yamaue H.et al: "Enhancement of tumor cell susceptibility to lymphckine-activated killer cells by treatment with the streptococcal preparation OK432." Biotherapy. 5. 83-93 (1992)

Yamaue H.et al：“通过链球菌制剂 OK432 治疗，增强肿瘤细胞对淋巴因子激活的杀伤细胞的敏感性。”

Hiroki Yamaue et al.: "Chemosensitivity testing of fresh human gastric cancer with highly purified fumor cells" British Journal of Cancer. 66. 794-799 (1992)

Hiroki Yamaue 等人：“用高度纯化的肿瘤细胞对新鲜人胃癌进行化学敏感性测试”英国癌症杂志。