Awwad M, North R J
Trudeau Institute, Inc. Saranac Lake, NY 12983.
Cancer Immunol Immunother. 1988;26(1):55-60. doi: 10.1007/BF00199848.
It was shown that sublethal (500 rads), whole-body gamma-irradiation of mice bearing an established i.d. immunogenic tumor can result, after several days delay, in complete tumor regression and long-term survival, but only if radiation is given after the tumor is established and growing progressively. Exposing mice to the same dose of radiation several hours after tumor cells were implanted resulted, in contrast, in enhanced growth of the primary tumor and in earlier death from systemic disease. Irradiation-induced tumor regression failed to occur in mice that were incapable of generating antitumor immunity, because of having been made T cell deficient by thymectomy and irradiation. Again, irradiation-induced tumor regression could be blocked by infusion of spleen cells from donor mice bearing a well-established tumor. These and previously published results support the view that sublethal, whole-body ionizing irradiation causes tumor regression by preferentially destroying radiosensitive suppressor T cells, thereby enabling the host to generate a therapeutic level of concomitant immunity. It is suggested that the preferential destruction of suppressor cells by irradiation depends on the acquisition, during immunologic induction, of radioresistance by antigen-activated effector T cells, and that this is the reason irradiation causes regression only of established tumors. Not all tumors tested were immunogenic enough to undergo regression in response to gamma-irradiation.
结果表明，对携带已形成的具有免疫原性肿瘤的小鼠进行亚致死剂量（500拉德）的全身γ射线照射，经过数天延迟后，可导致肿瘤完全消退并长期存活，但前提是在肿瘤形成并逐渐生长后再进行辐射。相反，在植入肿瘤细胞数小时后让小鼠接受相同剂量的辐射，则会导致原发性肿瘤生长加快，并因全身性疾病而更早死亡。由于通过胸腺切除和照射使T细胞缺乏，无法产生抗肿瘤免疫力的小鼠不会发生辐射诱导的肿瘤消退。同样，输注来自携带已形成肿瘤的供体小鼠的脾细胞可阻断辐射诱导的肿瘤消退。这些结果以及先前发表的结果支持以下观点：亚致死剂量的全身电离辐射通过优先破坏对辐射敏感的抑制性T细胞而导致肿瘤消退，从而使宿主能够产生治疗水平的伴随免疫。有人提出，辐射对抑制细胞的优先破坏取决于在免疫诱导过程中抗原激活的效应T细胞获得的辐射抗性，这就是辐射仅导致已形成肿瘤消退的原因。并非所有测试的肿瘤都具有足够的免疫原性，能够对γ射线照射产生消退反应。
