CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors.
Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors.
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皮肤犬肥大细胞瘤(ccMCTs)根据其分级在生物学行为、治疗和预后方面存在差异。免疫细胞浸润与某些人类癌症的预后和治疗反应相关,免疫靶向治疗在兽医肿瘤学中也日益受到探索。
然而,目前对ccMCTs肿瘤微环境(TME)的了解甚少。因此,本研究旨在确定低级别和高级别ccMCTs中T淋巴细胞、T调节淋巴细胞、PD-1+细胞和巨噬细胞的分布情况。研究纳入30例低级别和20例高级别福尔马林固定石蜡包埋的ccMCT样本。采用免疫组织化学(IHC)在连续切片上检测CD3、FOXP3、Iba1和PD-1。每例肿瘤选取CD3+细胞数量最多的三个400倍视野。使用ImageJ软件对这三个“热点”视野中CD3+、FOXP3+和Iba1+细胞的百分比以及PD-1+细胞的数量进行定量。与低级别ccMCTs相比,高级别ccMCTs中Iba1表达显著增高(均值 = 12.5% vs. 9.6%,p = 0.043)。PD-1表达总体较低,但高级别ccMCTs中观察到表达PD-1的细胞数量显著增多(中位数 1 vs. 0,p = 0.001)。不同级别ccMCTs之间CD3和FOXP3表达无显著差异。与低级别ccMCTs相比,高级别ccMCTs中巨噬细胞和PD-1+细胞更为常见。需要进一步研究以明确巨噬细胞和少量PD-1+细胞在高级别ccMCTs中的作用。
Cutaneous canine mast cell tumors (ccMCTs) vary in their biological behavior, treatment, and prognosis, based on their grade. Immune cell infiltration has been associated with prognosis and response to treatments in some human cancers, and immune-targeting therapeutics are increasingly being explored in veterinary oncology.
However, currently little is known about the tumor microenvironment (TME) in ccMCTs.
Therefore, the objective of this study was to determine the prevalence of T lymphocytes, T regulatory lymphocytes, PD-1+ cells and macrophages in low- and high-grade ccMCTs. Thirty low-grade and 20 high-grade formalin-fixed paraffin-embedded ccMCT samples were included. Immunohistochemistry (IHC) was performed to detect CD3, FOXP3, Iba1, and PD-1 on sequential sections. Three 400x fields with the highest numbers of CD3+ cells were identified for each tumor.
The percentage of CD3+, FOXP3+, and Iba1+ cells, and the number of PD-1+ cells, was quantified in each of these three "hot-spot" fields using ImageJ software. Iba1 expression was significantly greater in high-grade compared to low-grade ccMCTs (mean = 12. 5% vs. 9. 6%, p = 0. 043).
PD-1 expression was low overall, but a significantly higher number of PD-1-expressing cells was observed in high-grade ccMCTs (median 1 vs. 0, p = 0. 001). No significant difference was noted in CD3 and FOXP3 expression between ccMCT grades. Macrophages and PD-1+ cells were more frequent in high-grade, compared to low-grade ccMCTs.
Further studies are needed to define the role of macrophages and rare PD-1+ cells in high-grade ccMCTs.
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