Midis G P, Fabian D F, Lefor A T
Department of Surgery, University of Maryland, Baltimore 21201.
J Surg Res. 1992 May;52(5):530-6. doi: 10.1016/0022-4804(92)90323-r.
We have previously shown that the combination of immunotherapy with interleukin 2 (IL-2) and local hyperthermia (LHT) abrogates the growth of murine subcutaneous tumors significantly more than either modality alone. This study was undertaken to investigate whether the beneficial effect of combined modality therapy could be attributed to increased trafficking of effector cells to the tumor. After inducing MCA-105 sarcomas in the hindlimbs of C57BL/6 mice, animals were given no therapy, LHT, IL-2, or IL-2 + LHT followed by an iv injection of 51Cr-labeled syngeneic splenocytes or LAK cells. Select organs and the tumor-bearing extremity were counted in a gamma counter. IL-2 or LHT alone did not affect lymphocyte migration, while IL-2 + LHT significantly decreased trafficking (P less than 0.001) to the tumor. LAK cells showed increased migration to the tumor site compared to splenocytes in all treatment groups (P less than 0.02). IL-2 caused increased migration of LAK cells but not splenocytes to the lung; this was not affected by LHT. LAK cell trafficking to the spleen was decreased by IL-2 and IL-2 + LHT, while splenocyte migration was decreased in the LHT and combined treatment groups. LHT and IL-2 had no effect on trafficking of either effector cell type to liver or kidney. These results show that the beneficial effect of combined modality therapy may not be due to increased trafficking of lymphocytes to the tumor area. In addition, LAK cells traffic more to subcutaneous tumors than splenocytes, and this cannot be explained by the differential trafficking to other organs. The results of this study will be important in the planning of future experiments with combined adoptive immunotherapy and hyperthermia.
我们之前已经表明，免疫疗法与白细胞介素2（IL-2）和局部热疗（LHT）联合使用，比单独使用任何一种方法都能更显著地抑制小鼠皮下肿瘤的生长。本研究旨在调查联合治疗的有益效果是否可归因于效应细胞向肿瘤的迁移增加。在C57BL/6小鼠后肢诱导MCA-105肉瘤后，对动物不进行治疗、给予LHT、IL-2或IL-2 + LHT，随后静脉注射51Cr标记的同基因脾细胞或LAK细胞。在γ计数器中对选定器官和荷瘤肢体进行计数。单独使用IL-2或LHT不影响淋巴细胞迁移，而IL-2 + LHT显著减少（P小于0.001）向肿瘤的迁移。与所有治疗组中的脾细胞相比，LAK细胞向肿瘤部位的迁移增加（P小于0.02）。IL-2导致LAK细胞而非脾细胞向肺的迁移增加；这不受LHT影响。IL-2和IL-2 + LHT减少了LAK细胞向脾脏的迁移，而LHT和联合治疗组中脾细胞的迁移减少。LHT和IL-2对任何一种效应细胞类型向肝脏或肾脏的迁移均无影响。这些结果表明，联合治疗的有益效果可能并非由于淋巴细胞向肿瘤区域的迁移增加。此外，LAK细胞比脾细胞更多地迁移至皮下肿瘤，而这无法用向其他器官的差异迁移来解释。本研究结果对于未来联合过继性免疫疗法和热疗实验的规划具有重要意义。
