肿瘤细胞治疗研究
英文原题：Exploring predictive biomarkers of efficacy and survival with nivolumab treatment for unresectable/recurrent esophageal squamous cell carcinoma.
Exploring predictive biomarkers of efficacy and survival with nivolumab treatment for unresectable/recurrent esophageal squamous cell carcinoma.
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CD8+和 CCR8+细胞计数、CD8/Foxp3 和 CD8/CCR8 比值以及 TLS 密度可能是 PD-1 阻断治疗 ESCC 的疗效和生存的预测生物标志物。
程序性细胞死亡蛋白-1（PD-1）阻断改善了食管鳞状细胞癌（ESCC）患者的生存，但缓解率较低。迫切需要预测哪些患者将从PD-1阻断中获益的生物标志物。
这项多中心研究纳入了250例接受nivolumab作为二线或后线治疗的复发/不可切除晚期ESCC患者。我们通过免疫组织化学和苏木精/伊红染色，评估了手术标本和nivolumab治疗前内镜活检组织中的肿瘤浸润T淋巴细胞（TILs）和三级淋巴结构（TLS）密度。
在外科标本中，nivolumab的临床缓解（相对于无缓解）与CD8+淋巴细胞计数（160 vs. 95.2 cells/field，P = 0.0494）、CD8/Foxp3比值（6.52 vs. 2.72，P = 0.0053）和TLS密度（0.21/mm 2 vs. 0.10/mm 2，P = 0.0005）显著相关。在总生存期方面，多因素分析确定CD8/Foxp3比值（风险比[HR] = 1.83，P = 0.0050）和TLS密度（HR = 1.67，P = 0.0171）是外科标本中的独立预后参数。同样，在内镜活检中，nivolumab的临床缓解（相对于无缓解）与CD8+计数（254 cells/mm 2 vs. 124 cells/mm 2，P = 0.0344）、CCR8+淋巴细胞计数（62.6 cells/mm 2 vs. 140 cells/mm 2，P = 0.0355）、CD8/Foxp3比值（2.09 vs. 0.89，P = 0.040）和CD8/CCR8比值（2.34 vs. 0.89，P = 0.0020）显著相关。多因素分析还确定内镜活检中的CD8/CCR8比值（HR = 1.66，P = 0.0313）是独立预后参数。
Programmed cell death protein-1 (PD-1) blockade has improved survival for patients with esophageal squamous cell carcinoma (ESCC), but response rates are low. Biomarkers to predict who will benefit from PD-1 blockade are urgently needed.
This multicenter study involved 250 patients with recurrent/unresectable advanced ESCC receiving nivolumab as second- or later-line therapy. We assessed tumor-infiltrating T lymphocytes (TILs) and tertiary lymphoid structure (TLS) density using immunohistochemistry and hematoxylin/eosin staining in surgical specimens and pre-nivolumab endoscopic biopsies.
In surgical specimens, clinical response (vs. non-response) to nivolumab correlated significantly with CD8 + lymphocyte count (160 vs. 95.2 cells/field, P = 0.0494), CD8/Foxp3 ratio (6.52 vs. 2.72, P = 0.0053), and TLS density (0.21/mm 2 vs. 0.10/mm 2 , P = 0.0005). In terms of overall survival, multivariate analysis identified CD8/Foxp3 ratio (hazard ratio [HR] = 1.83, P = 0.0050) and TLS density (HR = 1.67, P = 0.0171 as independent prognostic parameters in surgical specimens. Similarly, in endoscopic biopsies, clinical response (vs. non-response) to nivolumab correlated significantly with CD8 + counts (254 cells/mm 2 vs. 124 cells/mm 2 , P = 0.0344), CCR8 + lymphocyte count (62.6 cells/mm 2 vs. 140 cells/mm 2 , P = 0.0355), CD8/Foxp3 ratio (2.09 vs. 0.89, P = 0.040), and CD8/CCR8 ratio (2.34 vs. 0.89, P = 0.0020). Multivariate analysis also identified CD8/CCR8 ratio in endoscopic biopsies (HR = 1.66, P = 0.0313) as an independent prognostic parameter.
CD8 + and CCR8 + cell counts, CD8/Foxp3 and CD8/CCR8 ratios, and TLS density may be predictive biomarkers of therapeutic efficacy and survival with PD-1 blockade for ESCC.
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