INTERLEUKIN-2 PRODUCTION BY TUMOR-CELLS BYPASSES T-HELPER FUNCTION IN THE GENERATION OF AN ANTITUMOR RESPONSE
INTERLEUKIN-2 PRODUCTION BY TUMOR-CELLS BYPASSES T-HELPER FUNCTION IN THE GENERATION OF AN ANTITUMOR RESPONSE
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DOI：
10.1016/0092-8674(90)90591-2
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发表时间：
1990-02-09
期刊：
影响因子：
64.5
通讯作者：
FROST, P
中科院分区：
文献类型：
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作者：
FEARON, ER;PARDOLL, DM;FROST, P
免疫原性差的小鼠结肠癌被用于研究抗肿瘤免疫的机制。注射通过基因转染工程化以分泌IL-2的肿瘤细胞刺激针对亲本肿瘤的MHC I类限制性溶细胞性T淋巴细胞（CTL）应答。分泌IL-2的肿瘤细胞在体内产生抗肿瘤反应，即使在缺乏CD 4 + T细胞的情况下。用工程化细胞免疫的动物被保护免于随后用亲本肿瘤细胞系的攻击。其他类型的肿瘤也有类似的发现。因此，以旁分泌方式提供辅助淋巴因子诱导肿瘤特异性免疫应答，包括内源性CTL和其他免疫效应细胞的活化。这些发现表明，有效的抗肿瘤免疫应答的失败可能主要是由于免疫系统的辅助臂缺陷，而不是缺乏肿瘤特异性细胞毒性效应细胞。此外，他们概述了一种增强肿瘤免疫力的新策略。
A poorly immunogenic murine colon cancer was used to investigate mechanisms of antitumor immunity. Injection of tumor cells engineered by gene transfection to secrete IL-2 stimulated an MHC class I-restricted cytolytic T lymphocyte (CTL) response against the parental tumor. The tumor cells secreting IL-2 produced an antitimor response in vivo, even in the absence of CD4+ T cells. Animals immunized with engineered cells were protected against subsequent challenge with the parental tumor cell line. Similar findings were demonstrated for other tumor types. Thus, provision of a helper lymphokine in a paracrine fashion induced a tumor-specific immune response involving activation of endogenous CTLs and other immune effector cells. These findings demonstrate that the failure of an effective antitumor immune response may be primarily due to a helper arm deficiency of the immune system rather than a paucity of tumor-specific cytotoxic effector cells. Furthermore, they outline a novel strategy for augmenting tumor immunity.