Fujita Kazutoshi, Kimura Go, Tsuzuki Toyonori, Kato Taigo, Banno Eri, Kazama Akira, Yamashita Ryo, Matsushita Yuto, Ishii Daisuke, Fukawa Tomoya, Nakagawa Yuki, Fukuyama Tamaki, Sano Fumikazu, Kondo Yukihiro, Uemura Hirotsugu
Department of Urology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
Department of Urology, Nippon Medical School, Tokyo 113-8603, Japan.
Cancers (Basel). 2022 Oct 26;14(21):5258. doi: 10.3390/cancers14215258.
Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.
已有报道称，同步性和异时性转移性肾细胞癌（mRCC）原发灶存在生物学或免疫学差异。然而，原发灶的肿瘤免疫微环境（TIME）与转移时间之间的关联仍不清楚。我们基于转移时间间隔，主要是同步组（SG；3个月内转移）和异时组（MG；3个月后转移），研究了mRCC患者原发灶TIME的差异及其与临床病理参数的关联。总体而言，568例一线接受血管内皮生长因子受体抑制剂治疗的患者构成了分析人群（SG：N = 307 [54.0%]；MG：N = 261 [46.0%]）。SG中具有预后不良病理特征肿瘤的患者比例更高：WHO/ISUP 4级、坏死、淋巴管侵犯、浸润性生长模式和肉瘤样分化。关于TIME，SG中比MG具有更多的免疫原性特征，PD-L1阳性率更高，无免疫表型比例更低。这是第一项基于转移时间间隔研究mRCC患者原发灶TIME差异的研究。原发灶的TIME可能会影响转移时间。
