Reciprocal changes in tumor antigenicity and antigen-specific T cell function during tumor progression.
Reciprocal changes in tumor antigenicity and antigen-specific T cell function during tumor progression.
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DOI：
10.1084/jem.20041240
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发表时间：
2004-12-20
影响因子：
15.3
通讯作者：
Marson, AL
中科院分区：
文献类型：
--
作者：
Zhou, G;Lu, ZB;McCadden, JD;Levitsky, HI;Marson, AL
存在两个看似不相容的模型来解释免疫活性宿主中癌症的进展。癌症免疫监视假说假设，免疫系统识别转化的细胞会产生效应反应，这可能会阻碍肿瘤的生长。临床上可检测到的癌症是由于逃脱了这种选择压力的肿瘤变种的出现。或者，诱导对肿瘤抗原的免疫耐受可能会使癌症进展。我们建立了一个模型，在该模型中，肿瘤特异性T细胞的功能和肿瘤抗原表达的变化可以在癌症进展过程中跟踪。早期对抗原的识别导致肿瘤特异性CD4+T细胞的激活、扩增和效应功能，导致表达显著降低的抗原水平的肿瘤的生长。然而，抗原丢失并不完全，水平仍然高于体内肿瘤特异性T细胞识别所需的阈值。面对持续存在的抗原，T细胞继而耐受，导致调节进一步抗原丢失的能力受损。总之，这些研究证实，免疫监视和肿瘤编辑的过程与肿瘤特异性T细胞功能谱系也被“编辑”的过程共存，这两个历史上对我们试图了解宿主抗肿瘤免疫至关重要的假设是一致的。
Two seemingly incompatible models exist to explain the progression of cancers in immunocompetent hosts. The cancer immunosurveillance hypothesis posits that recognition of transformed cells by the immune system results in the generation of an effector response that may impede tumor growth. Clinically detectable cancer results from the emergence of tumor variants that escape this selective pressure. Alternatively, induction of immune tolerance to tumor antigens may enable cancer progression. We established a model where changes in the function of tumor-specific T cells and in tumor antigen expression could be followed during cancer progression. Early recognition of antigen led to activation, expansion, and effector function in tumor-specific CD4+ T cells resulting in the outgrowth of tumors expressing substantially reduced levels of antigen. Antigen loss was not complete, however, and levels remained above the threshold required for tumor-specific T cell recognition in vivo. In the face of persisting antigen, T cell tolerance ensued, leading to an impaired ability to mediate further antigen loss. Together, these studies establish that the processes of immunosurveillance and tumor editing coexist with a process in which the functional tumor-specific T cell repertoire is also “edited,” reconciling two hypotheses historically central to our attempts to understand host antitumor immunity.
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DOI：
10.1084/jem.188.12.2357
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung K;Hayashi R;Lafond-Walker A;Lowenstein C;Pardoll D;Levitsky H
通讯作者：
Levitsky H
DOI：
10.1101/sqb.1999.64.429
发表时间：
1999-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Medzhitov, R;Janeway, CA
通讯作者：
Janeway, CA
影响因子：
15.3
作者：
Colella, T A;Bullock, T N;Russell, L B;Mullins, D W;Overwijk, W W;Luckey, C J;Pierce, R A;Restifo, N P;Engelhard, V H
通讯作者：
Engelhard, V H
影响因子：
82.9
作者：
Lee, PP;Yee, C;Davis, MM
通讯作者：
Davis, MM
影响因子：
82.9
作者：
Melcher, A;Todryk, S;Vile, RG
通讯作者：
Vile, RG