Alisauskas R M, Ponzio N M
Department of Pathology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark.
Cell Immunol. 1989 Apr 1;119(2):286-303. doi: 10.1016/0008-8749(89)90245-1.
Transplantable follicular center cell lymphomas of SJL/J mice are B-cell tumors that stimulate proliferation of host T-helper (TH) cells and which grow progressively in the peripheral lymphoid tissues of immunocompetent recipients. However, tumor growth is compromised in immunosuppressed syngeneic recipients, suggesting that the host response to SJL follicular center cell (SJL/FCC) lymphoma cells is required for optimal tumor growth. In vitro studies indicate that the host TH cells (Lyt-1+, 2-, L3T4a+) which respond to the major histocompatibility complex (MHC) class II (I-As) surface determinants on the SJL/FCC lymphoma cells produce a variety of lymphokines, some of which may promote tumor growth in vivo. The results of this study demonstrate that treatment of lymphoma-injected mice with L3T4a-specific mAb inhibits the growth of the SJL/FCC lymphoma cells, despite the fact that these tumor cells do not express L3T4a determinants. Thus, in this model, mAb therapy targeting host immune cells rather than the tumor cells is an effective means to control tumor growth. Long-term observation of SJL/FCC lymphoma-injected, anti-L3T4a mAb-treated mice reveals prolonged survival of the majority of these animals with periodic recurrence of tumor growth. During periods of remission, LN cells from these long-term surviving animals were unable to mount the characteristic in vitro host response to irradiated SJL/FCC lymphoma cells. These results provide direct evidence that SJL/FCC lymphoma cells fail to retain their characteristic neoplastic properties in a microenvironment that is initially devoid of tumor-responsive TH cells.
SJL/J小鼠的可移植滤泡中心细胞淋巴瘤是B细胞肿瘤，可刺激宿主T辅助（TH）细胞增殖，并在免疫活性受体的外周淋巴组织中逐渐生长。然而，在免疫抑制的同基因受体中肿瘤生长受到损害，这表明宿主对SJL滤泡中心细胞（SJL/FCC）淋巴瘤细胞的反应是肿瘤最佳生长所必需的。体外研究表明，对SJL/FCC淋巴瘤细胞上主要组织相容性复合体（MHC）II类（I-As）表面决定簇作出反应的宿主TH细胞（Lyt-1+、2-、L3T4a+）会产生多种淋巴因子，其中一些可能在体内促进肿瘤生长。本研究结果表明，用L3T4a特异性单克隆抗体治疗注射淋巴瘤的小鼠可抑制SJL/FCC淋巴瘤细胞的生长，尽管这些肿瘤细胞不表达L3T4a决定簇。因此，在该模型中，靶向宿主免疫细胞而非肿瘤细胞的单克隆抗体疗法是控制肿瘤生长的有效手段。对注射SJL/FCC淋巴瘤并经抗L3T4a单克隆抗体治疗的小鼠进行长期观察发现，这些动物中的大多数存活时间延长，但肿瘤生长会周期性复发。在缓解期，来自这些长期存活动物的淋巴结细胞无法对经辐照的SJL/FCC淋巴瘤细胞产生特征性的体外宿主反应。这些结果提供了直接证据，表明SJL/FCC淋巴瘤细胞在最初缺乏肿瘤反应性TH细胞的微环境中无法保持其特征性的肿瘤特性。
