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TIL(肿瘤浸润淋巴细胞)在接受抗程序性死亡配体 1(PD-L1)抗体治疗的犬口腔恶性黑色素瘤中的预后意义

英文原题:Prognostic Significance of Tumour Infiltrating Lymphocytes in Canine Oral Malignant Melanoma Treated With Anti-Programmed Cell Death Ligand 1 (PD-L1) Antibody Therapy.

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Prognostic Significance of Tumour Infiltrating Lymphocytes in Canine Oral Malignant Melanoma Treated With Anti-Programmed Cell Death Ligand 1 (PD-L1) Antibody Therapy.

PubMed 2026/02/12(内容时间) Vet Comp Oncol Q2 · IF 1.8(JCR 2025)

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中文摘要

免疫检查点抑制剂(ICI)已成为治疗犬口腔恶性黑色素瘤(OMM)的有前景策略,但仅部分病例出现临床应答。此外,兽医学中预测ICI疗效的生物标志物尚未确立。TIL(肿瘤浸润淋巴细胞)是人类ICI治疗的预测生物标志物。

本研究旨在探讨TIL对接受ICI治疗的犬OMM是否具有预测价值。研究对治疗前病理组织进行免疫组化,检测CD3阳性细胞(泛T细胞标志物)、颗粒酶B阳性细胞(细胞毒性T淋巴细胞或NK细胞标志物)及Foxp3阳性细胞(调节性T细胞标志物),并分析这些细胞的浸润模式及其对抗程序性细胞死亡配体1(PD-L1)抗体疗效的预后价值。不同TIL亚群浸润水平存在差异,犬OMM中观察到多种TIL浸润模式。生存分析显示,CD3阳性和颗粒酶B阳性细胞浸润高与无进展生存期和总生存期延长显著相关。

此外,反映细胞毒性细胞与调节性细胞平衡的免疫细胞组成比例也与生存时间显著相关。这些发现提示犬OMM具有与人类癌症类似的免疫表型。

总体而言,TIL特征有望成为接受抗PD-L1抗体治疗的犬OMM患者的重要预后生物标志物。

展开英文摘要原文

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy for canine oral malignant melanoma (OMM).

However, only a subset of cases have shown clinical responses.

Additionally, predictive biomarkers for the efficacy of ICIs in veterinary medicine are yet to be established. Tumour-infiltrating lymphocytes (TILs) are predictive biomarkers for ICI therapy in humans. In this study, we aimed to investigate the predictive utility of TILs for canine OMM treated with ICI therapy. Immunohistochemistry was performed on pre-treatment pathological tissues to detect cells positive for CD3 (pan-T cell marker), Granzyme B (cytotoxic T lymphocyte or natural killer cell marker) and Foxp3 (regulatory T cell marker).

Further, we analysed the infiltration patterns of these cells and their prognostic utility for anti-programmed cell death ligand 1 (PD-L1) antibody therapy. There were variances in the infiltration levels of each TIL subset; further, we observed several TIL infiltration patterns in canine OMM. Survival analysis revealed that high infiltration of CD3 + and Granzyme B + cells was significantly associated with prolonged progression-free survival and overall survival.

Furthermore, the immune cell composition ratio, which reflected the balance between cytotoxic and regulatory cells, was significantly associated with survival time.

These findings suggest that canine OMM exhibits immunological phenotypes analogous to those observed in human cancers. Taken together, the TIL profile holds significant potential as a prognostic biomarker for canine OMM treated with anti-PD-L1 antibody therapy.

论文信息

作者
Kamo S、Maekawa N、Kudo A、Yamauchi A、Yoshimoto S、Harada Y、Konnai S、Okagawa T
单位
Laboratory of Small Animal Surgery, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.Japan
期刊
Veterinary and comparative oncology2026 Jun
原文标识
PubMed 41681116 · DOI 10.1111/vco.70052