帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:Comparison of Tumor Microenvironments between Primary Tumors and Lymph Node Metastases in Head and Neck Squamous Cell Carcinoma and Their Predictive Role in Immune Checkpoint Inhibitor Treatment.
其 IP 在 12 例患者(57.1%)中不一致。
头颈部鳞状细胞癌(HNSCC)区域淋巴结转移(LNM)与原发肿瘤的肿瘤微环境(TME)之间关系尚不明确。本研究比较原发肿瘤与LNM中的TIL(肿瘤浸润淋巴细胞)及免疫表型(IP),后者根据TIL空间分布特征确定。研究纳入21例接受免疫检查点抑制剂(ICI)治疗且有区域LNM的HNSCC患者。配对比较原发肿瘤与LNM的TIL密度和IP发现,原发灶与LNM之间TIL密度无显著差异或相关性;12例患者(57.1%)的IP不一致。原发肿瘤和LNM中,肿瘤内TIL高的患者无进展生存期(PFS)均长于TIL低者(原发灶中位数5.2比1.3个月,P=0.003;LNM中位数30.2比1.3个月,P=0.012)。两处呈炎症型IP的患者PFS均长于非炎症型患者(原发灶中位数4.5比1.3个月,P=0.043;LNM中位数4.1比1.3个月,P=0.037)。鉴于TIL密度缺乏相关性、IP存在差异且两处TME均具有预测价值,评估HNSCC原发肿瘤及LNM的TME可能有助于精准使用ICI。原发肿瘤与LNM的TME显著不一致,并影响生存结局;因此同时评估两处TME可能有益于HNSCC精准免疫治疗。
The relationship between tumor microenvironments (TMEs) of regional lymph node metastases (LNMs) and primary tumors in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study compared tumor-infiltrating lymphocytes (TILs) and the immune phenotype (IP), characterized by spatial TIL distribution, between primary tumors and LNMs. Twenty-one HNSCC patients with regional LNM who received immune checkpoint inhibitors (ICIs) were included. A paired comparative analysis of TIL densities and IP between primary tumors and LNMs revealed no significant difference or correlation between TIL densities in primary tumors and LNMs. Their IPs were discordant in 12 patients (57.1%). Patients with high intratumoral TIL exhibited longer progression-free survival (PFS) than those with low intratumoral TIL in both primary tumors (median, 5.2 vs. 1.3 months, p = 0.003) and LNMs (median, 30.2 vs. 1.3 months, p = 0.012). Patients with inflamed IP exhibited longer PFS than those with non-inflamed IP in both primary tumors (median, 4.5 vs. 1.3 months, p = 0.043) and LNMs (median, 4.1 vs. 1.3 months, p = 0.037). Given the lack of correlation in TIL densities, the discrepancies in IP, and the predictive value of both TMEs, evaluating the TMEs of both primary tumors and LNMs may be beneficial for the precise use of ICIs in HNSCC. There was a significant discordance between the TME of primary tumors and LNMs, with implications in survival outcomes. Therefore, evaluating the TME of both the primary tumor and LNM could be beneficial for the precise use of ICIs in HNSCC.
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