Activity and Immune Correlates of Programmed Death-1 Blockade Therapy in Patients With Advanced Large Cell Neuroendocrine Carcinoma
Activity and Immune Correlates of Programmed Death-1 Blockade Therapy in Patients With Advanced Large Cell Neuroendocrine Carcinoma
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DOI：
10.1016/j.cllc.2021.02.003
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发表时间：
2021-07-30
影响因子：
3.6
通讯作者：
Motoi, Noriko
中科院分区：
文献类型：
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作者：
Shirasawa, Masayuki;Yoshida, Tatsuya;Motoi, Noriko
我们评估了抗程序性死亡受体1（PD-1）治疗晚期大细胞神经内分泌癌（LCNEC）患者的疗效。无论程序性死亡配体1（PD-L1）阳性与否，抗PD-1治疗均有效。肿瘤CD 8阳性肿瘤浸润淋巴细胞的密度和共存突变的存在可能是晚期LCNEC患者抗PD-1治疗疗效的预测因素。背景资料：抗程序性死亡受体1（PD-1）治疗在大细胞神经内分泌癌（LCNEC）患者中的疗效尚不清楚。我们通过评估免疫相关的肿瘤微环境来研究抗PD-1治疗的结果及其预测标志物。患者：我们回顾性分析了接受全身化疗的晚期LCNEC患者。我们还评估了PD配体1（PD-L1）表达（克隆：22 C3）、CD 8阳性肿瘤浸润淋巴细胞（TIL）和突变特征。结果：70例患者入组，其中13例接受抗PD-1治疗。抗PD-1治疗的无进展生存期（PFS）和客观缓解率（ORR）分别为4.2个月和39%。接受抗PD-1治疗的患者（n = 13）的总生存期显著优于未接受抗PD-1治疗的患者（n = 57）（25.2个月vs 10.9个月; P = 0.02）。在接受抗PD-1治疗的13名患者中，10名患者（90%）患有PD-L1阴性肿瘤。肿瘤CD 8阳性TIL密度高（>= 38/mm 2）的患者的ORR和PFS显著优于肿瘤CD 8阳性TIL密度低的患者（ORR：P = .02; PFS：P = .003）。此外，所有3例TP 53突变与PIK 3CA突变（8例患者中的2例）或RB 1突变（8例患者中的1例）共发生的患者对抗PD-1治疗有应答。结论：无论PD-L1阳性与否，抗PD-1治疗对晚期LCNEC患者均有效。我们的研究可能表明，肿瘤CD 8阳性TIL的密度和共存突变的存在是抗PD-1治疗晚期LCNEC患者疗效的预测因素。
We evaluated the efficacy of anti-programmed death receptor 1 (PD-1) therapy in patients with advanced large cell neuroendocrine carcinoma (LCNEC). Anti-PD-1 therapy was effective regardless of programmed death ligand 1 (PD-L1) positivity. The density of tumoral CD8-positive tumor-infiltrating lymphocytes and the presence of co-occurring mutations might be predictors of the efficacy of anti-PD-1 therapy in patients with advanced LCNEC. Background: The efficacy of anti-programmed death receptor 1 (PD-1) therapy in patients with large cell neuroendocrine carcinoma (LCNEC) remains unclear. We investigated the outcome of anti-PD-1 therapy and its predictive markers by evaluating the immune-related tumor microenvironment. Patients: We retrospectively reviewed patients with advanced LCNEC treated with systemic chemotherapy. We also evaluated PD ligand 1 (PD-L1) expression (clone: 22C3), CD8-positive tumor-infiltrating lymphocytes (TILs), and the mutational profiles. Results: Seventy patients were enrolled, and 13 of 70 patients received anti-PD-1 therapy. The progression-free survival (PFS) and objective response rate (ORR) of the anti-PD-1 therapy were 4.2 months and 39%, respectively. The overall survival of patients treated with anti-PD-1 therapy (n = 13) was significantly better than those treated without anti-PD-1 therapy (n = 57) (25.2 months vs 10.9 months; P = .02). Among the 13 patients treated with anti-PD-1 therapy, 10 patients (90%) had PD-L1-negative tumors. Patients with a high density of tumoral CD8-positive TILs ( >= 38/mm 2 ) had a significantly better ORR and PFS than those with a low density of tumoral CD8-positive TILs (ORR: P = .02; PFS: P = .003). Additionally, all 3 patients with TP53 mutation co-occurring with PIK3CA mutation (2 of 8 patients) or RB1 mutation (1 of 8 patients) responded to anti-PD-1 therapy. Conclusions: Anti-PD-1 therapy was effective regardless of PD-L1 positivity in patients with advanced LCNEC. Our investigation might suggest that the density of tumoral CD8-positive TILs and the presence of co-occurring mutations are predictors of the efficacy of anti-PD-1 therapy in patients with advanced LCNEC.