Prognostic role of the innate immune signature CD163 and “eat me” signal calreticulin in clear cell renal cell carcinoma
Prognostic role of the innate immune signature CD163 and “eat me” signal calreticulin in clear cell renal cell carcinoma
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先天免疫特征 CD163 和“吃我”信号钙网蛋白在透明细胞肾细胞癌中的预后作用
DOI：
10.1007/s00262-023-03369-8
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Oya Mototsugu
中科院分区：
文献类型：
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作者：
Anno Tadatsugu;Tanaka Nobuyuki;Takamatsu Kimiharu;Hakozaki Kyohei;Kufukihara Ryohei;Baba Yuto;Takeda Toshikazu;Matsumoto Kazuhiro;Morita Shinya;Kosaka Takeo;Mikami Shuji;Nishihara Hiroshi;Mizuno Ryuichi;Oya Mototsugu
天然免疫状态对肾透明细胞癌(CcRCC)患者的影响目前尚不清楚。我们在这里提供了更广泛的关于ccRCC免疫生物学内部图景的信息。总共获得了来自三个不同队列的260份ccRCC样本，其中包括213个原发肿瘤和47个转移瘤。我们重点研究了CD68、CD163、“吃我”信号钙网织蛋白、“不要吃我”信号CD47和信号调节蛋白α这五个具有代表性的先天免疫信号，并通过免疫组织化学定量检测了每个信号的作用。然后，我们通过下一代测序进行了完整的基因组突变分析。在5种标志物中，CD163高表达和钙网蛋白低表达预示着ccRCC的预后。先天免疫风险组(高危：高CD163/低钙网织蛋白，中危：高CD163/高钙网织蛋白或低CD163/低钙网织蛋白，低风险：低CD163/高钙网织蛋白，低风险：低CD163/高钙网织蛋白)的应用使患者预后和恶性程度的顺序分层成为可能。尽管观察到了器官特异性的差异，但转移似乎具有更高的先天免疫风险，尤其是在肺部，根据我们的风险评分，50%的ccRCC转移被归类为高危组。基于先天免疫风险组的基因组改变分析显示，根据两个先天免疫特征CD163和钙网蛋白，TP53/细胞周期途径的改变在高危ccRCC患者中非常普遍。本研究结果为研究ccRCC肿瘤天然免疫的免疫基因组生物学提供了洞察力，并将有助于未来针对实体肿瘤天然免疫系统的治疗。
The effects of the innate immune status on patients with clear cell renal cell carcinoma (ccRCC) currently remain unknown. We herein provided more extensive information about the inner landscape of immunobiology of ccRCC. In total, 260 ccRCC samples from three different cohorts consisting of 213 primary tumors and 47 metastases were obtained. We focused on five representative innate immune signatures, CD68, CD163, the “eat me” signal calreticulin, the “don't eat me” signal CD47, and signal regulatory protein α, and examined the role of each signature by quantitative immunohistochemistry. We then conducted an integrated genome mutation analysis by next-generation sequencing. Among the five markers, high CD163 and low calreticulin expression levels were prognostic in ccRCC. The application of a new risk model based on CD163 and calreticulin levels, named the innate immune risk group (high risk: high-CD163/low calreticulin, intermediate risk: high-CD163/high calreticulin or low CD163/low calreticulin, low risk: low-CD163/high calreticulin), enabled the sequential stratification of patient prognosis and malignancy. Although organ-specific differences were observed, metastases appeared to have a higher innate immune risk, particularly in the lungs, with 50% of ccRCC metastases being classified into the high-risk group according to our risk score. An analysis of genomic alterations based on the innate immune risk group revealed that alterations in the TP53/Cell cycle pathway were highly prevalent in high-risk ccRCC patients according to two innate immune signatures CD163 and calreticulin. The present results provide insights into the immune-genomic biology of ccRCC tumors for innate immunity and will contribute to future therapies focused on the innate immune system in solid cancers.
影响因子：
1.8
作者：
Ma, Chaoya;Horlad, Hasita;Komohara, Yoshihiro
通讯作者：
Komohara, Yoshihiro