Kadomoto Suguru, Izumi Kouji, Hiratsuka Kaoru, Nakano Taito, Naito Renato, Makino Tomoyuki, Iwamoto Hiroaki, Yaegashi Hiroshi, Shigehara Kazuyoshi, Kadono Yoshifumi, Nakata Hiroki, Saito Yohei, Nakagawa-Goto Kyoko, Mizokami Atsushi
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.
Department of Histology and Cell Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.
Cancers (Basel). 2020 Feb 4;12(2):354. doi: 10.3390/cancers12020354.
We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use "M1-like" and "M2-like" to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...].
我们感谢津斯和亚伯拉罕[1]对我们研究CCL20-CCR6轴在肾细胞癌（RCC）细胞中的作用的论文发表评论[2]。正如他们所指出的，我们的研究存在一定局限性。虽然M1型和M2型无法明确区分，且它们之间可能存在特征的连续变化，但据报道，多种特异性标志物在M1型和M2型细胞上表达。遗憾的是，我们的研究未证实M1和M2巨噬细胞之间存在明确差异。为了实现更多的分化，可能需要像津斯和亚伯拉罕评论中所建议的那样进行多种刺激。因此，我们需要权宜地使用“M1样”和“M2样”来提及这些巨噬细胞样细胞的特定状态。同时，与RCC细胞共培养的M2样THP-1细胞的CCL20表达水平与亲本THP-1细胞相比显著升高，这表明肿瘤微环境中的某些刺激而非理论刺激使巨噬细胞发生分化；然而，需要进一步研究使用更合适的模拟肿瘤微环境的共培养系统来阐明这一机制。CCL20和M2标志物的免疫组织化学将有助于更好地理解组织浸润巨噬细胞的作用，甚至据报道组织CD68染色强度本身与RCC患者的预后相关[3]。[...]
