巨噬细胞是免疫反应中的下游效应关键的执行者,在癌症发生过程中,巨噬细胞同样对于肿瘤微环境中的炎症反应具有重要的影响。近年来开发出的各类抗肿瘤疗法(化疗,放射性治疗,靶向药物,免疫疗法等)其最终的效应大多是通过肿瘤相关巨噬细胞(Tumor Associated Macrophages,TAM)的功能实现的。由于化疗与放疗可能会对巨噬细胞产生双面面的影响(好的方面:促进肿瘤的清除;坏的方面:耐药性等)。因此,对TAM的深入了解对于我们发展肿瘤治疗手段是十分必要的。" n2 \* E. E- @" s
1 X# x5 t- H: ~另外,如一些细菌类似物,TLR的激活剂等也在临床前与临床的试验中。一种完全人源化的CD40阻断型抗体CD40配合化疗在治疗胰腺癌病人的临床试验中效果显著。在小鼠胰腺癌模型中,CD40阻断型抗体能够有效提高APC表面MHC-II与CD86的表达量。在其它方面,有一些趋化因子可以促进巨噬细胞向肿瘤微环境中迁移。 ) X/ l! L9 z9 x: r- r . T! H" S2 i% W* a% b7 k
根据以上内容,作者提出了围绕TAM设计新的癌症治疗手段的新观点。(资讯来源:生物谷) $ y- l% d# r$ U. C) [0 ]+ b
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doi: 10.1084/jem.20150295 ! P ^, p8 k0 W1 ~8 i / | g' D: V+ P
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The interaction of anticancer therapies with tumor-associated macrophages, G, |0 O4 t' d5 y$ R& S) N9 k
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Alberto Mantovani and Paola Allavena " `, G4 I' @% e8 z* w 8 H9 g; Z d- C' G* t
Macrophages are essential components of the inflammatory microenvironment of tumors. Conventional treatment modalities (chemotherapy and radiotherapy), targeted drugs, antiangiogenic agents, and immunotherapy, including checkpoint blockade, all profoundly influence or depend on the function of tumor-associated macrophages (TAMs). Chemotherapy and radiotherapy can have dual influences on TAMs in that a misdirected macrophage-orchestrated tissue repair response can result in chemoresistance, but in other circumstances, TAMs are essential for effective therapy. A better understanding of the interaction of anticancer therapies with innate immunity, and TAMs in particular, may pave the way to better patient selection and innovative combinations of conventional approaches with immunotherapy. 9 g! ?, M. B/ S, _5 o# J" l Q. W " {! r% q7 M2 V2 P# ^, X