Ghosh Dipanjan, Maiti Tapas K
Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India.
Immunobiology. 2007;212(8):667-73. doi: 10.1016/j.imbio.2007.05.005. Epub 2007 Jul 3.
Tumor-associated macrophages (TAMs) have a complex and ambivalent relationship with tumor progression and elimination. Though TAMs are reported to have pro- and anti-tumor roles, upon modification and activation TAMs can develop tumoricidal activities and thus might have applications in cancer therapy. Various immunomodulatory compounds could be used to modulate TAMs. In this study we used Abrus agglutinin, a plant lectin, in its native and heat-denatured forms, to investigate its effect on TAMs in Dalton's lymphoma-bearing mice. We found that treatment with both native (NA) and heat-denatured agglutinin (HDA) activated the TAMs, which showed significantly increased in vitro cytotoxicity towards tumor cells and production of nitric oxide but no difference in TNF-alpha production. The tumoricidal activities of both NA and HDA were dependent upon the activation of TAMs as in macrophage-depleted Dalton's lymphoma-bearing mice NA and HDA treatment could not decrease the number of tumor cells significantly. Thus, NA and HDA could be used as modulators of TAMs, for their therapeutic use in cancer.
肿瘤相关巨噬细胞(TAM)与肿瘤进展及清除之间存在复杂且矛盾的关系。尽管据报道TAM具有促肿瘤和抗肿瘤作用,但经过修饰和激活后,TAM可产生杀肿瘤活性,因此可能在癌症治疗中具有应用价值。多种免疫调节化合物可用于调节TAM。在本研究中,我们使用了植物凝集素相思子凝集素及其热变性形式,来研究其对荷道尔顿淋巴瘤小鼠体内TAM的影响。我们发现,天然(NA)和热变性凝集素(HDA)处理均可激活TAM,TAM对肿瘤细胞的体外细胞毒性显著增加,一氧化氮产生增多,但肿瘤坏死因子-α的产生无差异。NA和HDA的杀肿瘤活性均依赖于TAM的激活,因为在巨噬细胞耗竭的荷道尔顿淋巴瘤小鼠中,NA和HDA处理不能显著减少肿瘤细胞数量。因此,NA和HDA可作为TAM的调节剂,用于癌症治疗。