Tumour‐infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumour‐infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow‐up data were collected from 231 patients with mRCC; TIMs (mast cells density positive to tryptase), along with CD8⁺ and CD4⁺ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log‐rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression‐free survival (OS, P = .008, and PFS, P = .016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR = 0.624, 95% CI: 0.420‐0.927, P = .020) and PFS (HR = 0.658, 95% CI: 0.466‐0.930, P = .019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one‐ and two‐year OS (P = .002 and P = .004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8⁺ and CD4⁺ TILs (P = .008 and P = .001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co‐existence of CD8⁺ and CD4⁺ TILs, which have anti‐tumour effects on activation status.

中文翻译：

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转移性肾细胞癌的肥大细胞密度：与预后和肿瘤浸润淋巴细胞的关系

据报道，肿瘤浸润性肥大细胞（TIMs）在肿瘤微环境中发挥功能性作用。但是，关于它们对不同癌症的影响，存在有争议的证据。为了研究它们在转移性肾细胞癌（mRCC）中的作用，我们研究了TIMs的预后价值及其与舒尼替尼或索拉非尼治疗的mRCC患者的肿瘤浸润淋巴细胞（TIL）的关联。从231例mRCC患者中收集了基线临床特征和随访数据。TIM（肥大细胞密度对类胰蛋白酶呈阳性），以及CD8 ⁺和CD4 ⁺使用组织微阵列通过免疫组织化学评估TIL。对数秩检验以及单因素和多因素COX回归模型用于生存分析。我们的结果表明，肥大细胞密度高的患者 比低肥大细胞密度的患者具有更好的总体生存率和无进展生存率（OS，P  = .008，PFS，P = .016）。此外，多变量Cox回归分析鉴定的TIM作为独立的预后因素对OS（HR = 0.624，95％CI：0.420-0.927，P  = 0.020）和PFS（HR = 0.658，95％CI：0.466-0.930，P = .019）。此外，将TIM与国际mRCC数据库联合会（IMDC）风险模型相结合，可以实现一年和两年OS的统计显着性和更好的预测能力（分别为P  = .002和P  = .004）。此外，肥大细胞密度高的病例与CD8 ⁺和CD4 ⁺ TILs的高密度有关（分别为P  = 0.008和P  = 0.001）。因此，表现出肥大细胞密度高的mRCC患者的OS更好可能归因于CD8 ⁺和CD4 ⁺ TIL的共存，它们对激活状态具有抗肿瘤作用。