Charak B S, Sadowski R M, Mazumder A
Bone Marrow Transplantation Program, Georgetown University, Washington, D.C. 20057.
Cancer Res. 1992 Dec 1;52(23):6482-6.
Interferon (IFN) increases the expression of major histocompatibility (MHC) antigens on the surface of tumor cells. Cyclosporine A (CsA) administration following myeloablative therapy and syngeneic bone marrow transplantation results in the generation of cells with autoreactive and antitumor effects that are related to the expression of MHC antigens. We used these two agents following conventional chemotherapy in a non-bone marrow transplantation setting for a melanoma in a murine model. Treatment with IFN alone or CsA alone was ineffective in controlling the dissemination of melanoma. A combination therapy with both these agents resulted in a significant control in the dissemination of the tumor, prolonged the survival of the tumor-bearing mice over that with chemotherapy alone, and generated cells with potent MHC-unrestricted cytotoxic potential in vitro. Adoptive transfer of these cells to secondary tumor bearers treated with chemotherapy showed potent antitumor effect; in the absence of chemotherapy, these cells had no antitumor effect in the secondary recipients. The antitumor effect of cells generated by IFN plus CsA therapy following chemotherapy could be blocked by normal spleen cells. These data suggest that treatment with IFN plus CsA following nonmyeloablative chemotherapy generates cells with MHC-unrestricted cytotoxicity; this effect may be related to abolition of suppressor influences by the chemotherapy.
干扰素（IFN）可增加肿瘤细胞表面主要组织相容性（MHC）抗原的表达。在清髓性治疗和同基因骨髓移植后给予环孢素A（CsA），可产生具有自身反应性和抗肿瘤作用的细胞，这些作用与MHC抗原的表达有关。我们在非骨髓移植环境下，于传统化疗后在小鼠黑色素瘤模型中使用了这两种药物。单独使用IFN或单独使用CsA治疗在控制黑色素瘤扩散方面均无效。这两种药物联合治疗可显著控制肿瘤扩散，使荷瘤小鼠的生存期比单独化疗延长，并在体外产生具有强大的MHC非限制性细胞毒性潜能的细胞。将这些细胞过继转移至接受化疗的继发荷瘤小鼠，显示出强大的抗肿瘤作用；在无化疗的情况下，这些细胞在继发受体中无抗肿瘤作用。化疗后IFN加CsA治疗产生的细胞的抗肿瘤作用可被正常脾细胞阻断。这些数据表明，非清髓性化疗后使用IFN加CsA治疗可产生具有MHC非限制性细胞毒性的细胞；这种作用可能与化疗消除抑制性影响有关。
