Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Department of Immuno-Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
J Immunother Cancer. 2021 Mar;9(3). doi: 10.1136/jitc-2020-002009.
Circulating cytokines and angiogenic factors have been associated with clinical outcomes in patients with metastatic renal cell carcinoma (RCC) receiving systemic therapy. However, none have yet examined cytokine concentrations in parallel cohorts receiving either immunotherapy or targeted therapy.
In this prospective correlative study, we enrolled 56 patients who were planned for treatment with either a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or immune checkpoint inhibitor (ICI). Eligibility requirements permitted any RCC histologic subtype, International Metastatic Renal Cell Carcinoma risk classification, and line of therapy. Immunologic profile was assessed at baseline and after 1 month on treatment using a Human Cytokine 30-plex protein assay (Invitrogen). Clinical benefit was defined as complete response, partial response, or stable disease ≥6 months per RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria.
Clinical benefit was similar between VEGF-TKI and ICI arms (65% vs 54%). Patients with clinical benefit from VEGF-TKIs had lower pretreatment levels of interleukin-6 (IL-6) (p=0.02), IL-1RA (p=0.03), and granulocyte colony-stimulating factor (CSF) (p=0.02). At 1 month, patients with clinical benefit from ICIs had higher levels of interferon-γ (IFN-γ) (p=0.04) and IL-12 (p=0.03). Among patients on VEGF-TKIs, those with clinical benefit had lower 1 month IL-13 (p=0.02) and granulocyte macrophage CSF (p=0.01) as well as higher 1 month VEGF (p=0.04) compared with patients with no clinical benefit.
For patients receiving VEGF-TKI or ICI therapy, distinct plasma cytokines were associated with clinical benefit. Our findings support additional investigation into plasma cytokines as biomarkers in metastatic RCC.
循环细胞因子和血管生成因子与接受系统治疗的转移性肾细胞癌（RCC）患者的临床结局相关。然而，目前还没有研究同时检测接受免疫治疗或靶向治疗的平行队列中的细胞因子浓度。
在这项前瞻性相关研究中，我们纳入了 56 名计划接受血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKI）或免疫检查点抑制剂（ICI）治疗的患者。入选标准允许任何 RCC 组织学亚型、国际转移性肾细胞癌危险分层和治疗线。使用人细胞因子 30 合子蛋白检测试剂盒（Invitrogen）在基线和治疗 1 个月后评估免疫谱。临床获益定义为完全缓解、部分缓解或根据 RECIST（实体瘤反应评估标准）V.1.1 标准≥6 个月的稳定疾病。
VEGF-TKI 和 ICI 组的临床获益相似（65% vs. 54%）。从 VEGF-TKI 中获益的患者，其治疗前白细胞介素 6（IL-6）（p=0.02）、白细胞介素 1 受体拮抗剂（IL-1RA）（p=0.03）和粒细胞集落刺激因子（CSF）（p=0.02）水平较低。从 ICIs 中获益的患者，其治疗后 1 个月干扰素-γ（IFN-γ）（p=0.04）和白细胞介素 12（IL-12）（p=0.03）水平较高。在接受 VEGF-TKI 治疗的患者中，与无临床获益的患者相比，有临床获益的患者在治疗后 1 个月 IL-13（p=0.02）和粒细胞巨噬细胞 CSF（p=0.01）水平较低，而 VEGF（p=0.04）水平较高。
对于接受 VEGF-TKI 或 ICI 治疗的患者，不同的血浆细胞因子与临床获益相关。我们的研究结果支持进一步研究血浆细胞因子作为转移性 RCC 的生物标志物。
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