Kreider J W, Bartlett G L, Christensen N D, Welsh P
Int J Cancer. 1985 Aug 15;36(2):217-24. doi: 10.1002/ijc.2910360214.
Rats cured of poorly immunogenic 13762A tumor by a combination of surgery and cyclophosphamide (CY) treatments produced peritoneal exudate cells (PEC) that prevented tumor growth when transferred to naive recipients, but they were ineffective against established tumor. A highly immunogenic 13762A clone (18A) induced PEC lymphocytes that completely reversed the growth of established primary tumor and of lymph-node metastases. 18A-immune PEC alone strongly inhibited tumors of 7 days' duration, but only moderately suppressed 14-day tumors, and had no effect on 21-day tumors. Irradiation (450 R) of rats prior to tumor transplantation improved the effectiveness of the PEC given at 7 days, but the benefit had gone by 14 days. Long-term T-cell depletion prior to tumor challenge allowed PEC inhibition of 7- and 14-day tumors, but not 21-day tumors. The most potent strategy was the administration of 450 R followed immediately by immune PEC. When rats with 21-day tumors were so treated, the metastases grew temporarily to a maximum diameter of 2-5 cm and then completely regressed. We concluded that a combination of immune T cells and 450 R can cure established, massive metastases, probably through a combination of an increase in the numbers of T-cell effectors and elimination of suppressor cells.
通过手术和环磷酰胺(CY)联合治疗治愈低免疫原性13762A肿瘤的大鼠产生了腹膜渗出细胞(PEC),当将这些细胞转移到未接触过该肿瘤的受体时可阻止肿瘤生长,但对已形成的肿瘤无效。一种高免疫原性的13762A克隆(18A)诱导的PEC淋巴细胞可完全逆转已形成的原发性肿瘤和淋巴结转移瘤的生长。单独的18A免疫PEC可强烈抑制7天龄的肿瘤,但仅适度抑制14天龄的肿瘤,对21天龄的肿瘤则无作用。在肿瘤移植前对大鼠进行照射(450伦琴)可提高7天时给予的PEC的有效性,但这种益处到14天时就消失了。在肿瘤攻击前长期耗竭T细胞可使PEC抑制7天龄和14天龄的肿瘤,但不能抑制21天龄的肿瘤。最有效的策略是立即给予450伦琴照射,随后给予免疫PEC。当对患有21天龄肿瘤的大鼠进行这种治疗时,转移瘤暂时生长至最大直径2至5厘米,然后完全消退。我们得出结论,免疫T细胞和450伦琴照射联合使用可能通过增加T细胞效应细胞数量和消除抑制细胞的组合来治愈已形成的大量转移瘤。