Radiotherapy potentiates the therapeutic efficacy of intratumoral dendritic cell administration.
Radiotherapy potentiates the therapeutic efficacy of intratumoral dendritic cell administration.
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DOI：
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发表时间：
2003-12
期刊：
影响因子：
11.2
通讯作者：
S. Teitz-Tennenbaum;Qiao Li;Susan D. Rynkiewicz;Fumito Ito;Mary A Davis;C. Mcginn;A. Chang
中科院分区：
文献类型：
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作者：
S. Teitz-Tennenbaum;Qiao Li;Susan D. Rynkiewicz;Fumito Ito;Mary A Davis;C. Mcginn;A. Chang
我们研究了放射治疗(RT)是否能提高以树突状细胞(DC)为基础的肿瘤免疫治疗的疗效。携带SC的小鼠。D5黑色素瘤或MCA 205肉瘤采用瘤内注射治疗。注射骨髓来源的非脉冲树突状细胞结合局部分割肿瘤照射。DC单独给药对D5肿瘤生长有轻微抑制作用，对MCA205无影响。单纯放疗对这两种肿瘤都有适度的抑制作用。DC联合RT对D5和MCA205肿瘤生长的抑制作用分别为相加和协同作用。在这两种肿瘤模型中，RT增强了DC给药的抗肿瘤效果，而不依赖于肿瘤内的细胞凋亡或坏死。综合治疗I.T.DC+RT优于S.C.肿瘤裂解物致敏的树突状细胞联合白介素2注射抑制D5肿瘤生长和延长小鼠生存时间。小鼠脾细胞经I.T.与对照组相比，DC+RT组含有更多的肿瘤特异性、分泌干扰素-γ的T细胞。此外，过继转移这些脾细胞在已确定肺转移的小鼠中介导了显著的肿瘤消退。联合治疗后切除残存的S.C.肿瘤对随后的静脉注射具有保护性免疫作用。肿瘤挑战。此外，IT。DC加RT治疗S.C.同时伴有肺转移的小鼠的肿瘤导致肺肿瘤显著减少。IT。DC联合RT可诱导荷瘤小鼠局部和全身有效的抗肿瘤反应。这种新的治疗方案可能对人类癌症的治疗有益。
We examined whether radiotherapy (RT) could enhance the efficacy of dendritic cell (DC)-based immunotherapy of cancer. Mice bearing s.c. D5 melanoma or MCA 205 sarcoma tumors were treated with intratumoral (i.t.) injections of bone marrow-derived unpulsed DCs in combination with local fractionated tumor irradiation. DC administration alone slightly inhibited D5 tumor growth and had no effect on MCA 205. RT alone caused a modest inhibition of both tumors. DC administration combined with RT inhibited D5 and MCA 205 tumor growth in an additive and synergistic manner, respectively. In both tumor models, RT intensified the antitumor efficacy of DC administration independent of apoptosis or necrosis within the tumor mass. Combination treatment of i.t. DCs plus RT was superior to s.c. injections of tumor lysate-pulsed DCs plus interleukin 2 in inhibiting D5 tumor growth and prolonging survival of mice. Splenocytes from mice treated with i.t. DCs plus RT contained significantly more tumor-specific, IFN-gamma-secreting T cells compared with control groups. Moreover, adoptive transfer of these splenocytes mediated significant tumor regression in mice bearing established pulmonary metastases. Combined treatment followed by resection of residual s.c. tumor conferred protective immunity against a subsequent i.v. tumor challenge. Furthermore, i.t. DC plus RT treatment of s.c. tumor in mice bearing concomitant pulmonary metastases resulted in a significant reduction of lung tumors. i.t. DC administration combined with RT induces a potent local and systemic antitumor response in tumor-bearing mice. This novel regimen may be beneficial in the treatment of human cancers.