Levey D L, Srivastava P K
Department of Biological Sciences, Fordham University, Bronx, New York 10458, USA.
J Exp Med. 1995 Oct 1;182(4):1029-36. doi: 10.1084/jem.182.4.1029.
Loss of T cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. In the present study, we have examined this and related phenomenon extensively in a large number of tumor-bearing mice, analyzed individually. Splenic T cells from tumor-bearing mice were isolated and characterized with respect to the following: (a) levels of three tyrosine kinases, p56lck, p59fyn, and ZAP-70; (b) expression of CD3-zeta; (c) alloreactive responses; and (d) antigen-specific responses. Contrary to recent reports, T cells from tumor-bearing mice were observed to express normal levels of lck, fyn, ZAP-70, and CD3-zeta. Further, T cells showed healthy alloreactive and antigen-specific responses until approximately 3 wk after post tumor challenge, when the tumors constituted approximately 20% of the body weight. Alterations with respect to some parameters were observed only in mice that had been bearing larger tumors for a considerably longer period. As human tumors are unlikely to grow to such large sizes (e.g., > 20% of the total body weight), the significance of the alterations in T cell expression of lck, fyn, ZAP-70, or CD3-zeta in the immune status of cancer patients is unclear. Altogether, these results indicate that alterations in T cell signal transduction molecules do not account for the profound tumor-specific suppression observed during tumor growth.
T细胞相关信号转导分子的缺失最近被认为与荷瘤宿主的免疫抑制有关。在本研究中,我们在大量单独分析的荷瘤小鼠中广泛研究了这一现象及相关现象。分离荷瘤小鼠的脾T细胞,并对其进行以下特征分析:(a)三种酪氨酸激酶p56lck、p59fyn和ZAP-70的水平;(b)CD3-zeta的表达;(c)同种异体反应性;(d)抗原特异性反应。与最近的报道相反,观察到荷瘤小鼠的T细胞表达正常水平的lck、fyn、ZAP-70和CD3-zeta。此外,直到肿瘤接种后约3周,当肿瘤占体重约20%时,T细胞都表现出正常的同种异体反应性和抗原特异性反应。仅在携带较大肿瘤较长时间的小鼠中观察到某些参数的改变。由于人类肿瘤不太可能长到如此大的尺寸(例如,>总体重的20%),因此lck、fyn、ZAP-70或CD3-zeta在T细胞表达中的改变对癌症患者免疫状态的意义尚不清楚。总之,这些结果表明,T细胞信号转导分子的改变并不能解释肿瘤生长过程中观察到的深刻的肿瘤特异性抑制。