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TIL(肿瘤浸润淋巴细胞)对晚期非小细胞肺癌一线帕博利珠单抗疗效的预后意义

英文原题:Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer.

查看英文原题

Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer.

PubMed 2023/01/20(内容时间) Discov Oncol Q3 · IF 2.8(JCR 2025)

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研究概要

间质 CD4 TIL 被确定为预测 pembrolizumab 治疗后 PFS 的重要标志物,尤其是在非腺癌和高 PD-L1 表达的患者中。此外,肿瘤内 CD8 TIL 被确定为 OS 的重要预测因子。

研究思路结论见上方概要

肿瘤和间质中的TIL(肿瘤浸润淋巴细胞)(TILs)有望准确预测程序性死亡-1(PD-1)阻断治疗的疗效。然而,对于TILs在一线PD-1治疗中的预后意义知之甚少。我们评估了在姑息治疗背景下接受pembrolizumab治疗的晚期或转移性非小细胞肺癌(NSCLC)患者中的TILs。

作为单中心回顾性研究,对107例NSCLC患者的肿瘤标本进行了TILs(CD4、CD8、Foxp3和PD-1)的多重免疫组化染色以及肿瘤和间质中CK和PD-L1的免疫组化染色,并与临床结局进行相关性分析。在一线pembrolizumab治疗前,通过活检(N = 93)或手术切除(N = 14)评估TILs和programmed death ligand-1(PD-L1)。

基质CD4 TIL数量低与骨转移和较差的行为状态(PS)显著相关。基质CD4 TIL数量高的患者的中位无进展生存期(PFS)和总生存期(OS)显著高于低浸润患者(分别为336天和731天 vs 204天和333天)。瘤内CD8 TIL数量高的患者(731天)OS显著优于低浸润患者(333天),但PFS无显著差异。多因素分析证实,基质CD4 TIL是PFS的独立预测因子,但不是OS的独立预测因子。此外,瘤内CD8 TIL是更好OS的独立预测因子。在关键亚组的生存分析中,基质CD4 TIL被确定为非腺癌组织学类型和PD-L1 ≥ 50%患者生存的显著预测因子。

展开英文摘要原文

Multiplex immunohistochemistry staining of TILs (CD4, CD8, Foxp3, and PD-1) and immunohistochemical staining of CK and PD-L1 in the tumor and stroma was performed in tumor specimens of 107 NSCLC patients and correlated with clinical outcomes, as a single-center retrospective study. TILs and programmed death ligand-1 (PD-L1) were assessed on biopsies (N = 93) or surgical resections (N = 14) before first-line pembrolizumab.

A low number of stromal CD4 TILs were significantly associated with bone metastasis and poor performance status (PS). The median progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with a high number of stromal CD4 TILs (336 days and 731 days, respectively) than in those with low infiltration (204 days and 333 days, respectively). Patients with a high number of intratumoral CD8 TILs (731 days) yielded significantly better OS than those with low infiltration (333 days), but not for PFS. Multivariate analysis confirmed that stromal CD4 TILs were independent predictors of PFS, but not OS. Furthermore, intratumoral CD8 TILs were independent predictors of better OS. In the survival analysis of key subgroups, stromal CD4 TILs were identified as significant predictors of survival in patients with non-adenocarcinomatous histology and PD-L1 ≥ 50%.

Stromal CD4 TILs were identified as a significant marker for predicting the PFS after pembrolizumab therapy, especially in patients with non-adenocarcinoma and high PD-L1 expression. In addition, intratumoral CD8 TILs were identified as significant predictors of OS.

论文信息

作者
Kaira K、Yamaguchi O、Kawasaki T、Hashimoto K、Miura Y、Shiono A、Mouri A、Imai H
单位
Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan. kkaira1970@yahoo.co.jp.Japan
期刊
Discover oncology2023 Jan 20
原文标识
PubMed 36662367 · DOI 10.1007/s12672-023-00615-4