Tumor immune microenvironment in odontogenic carcinomas: Evaluation of the therapeutic potential of immune checkpoint blockade

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine Pub Date : 2024-03-06 DOI:10.1111/jop.13525

Kyu-Young Oh, Seong-Doo Hong, Hye-Jung Yoon

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引用次数: 0

Abstract

Background

Despite recent advances in the use of immune checkpoint blockade (ICB) across various cancer types, its efficacy in odontogenic carcinomas remains unexplored. This study aims to investigate PD-L1 expression and the tumor immune microenvironment (TIME) in odontogenic carcinomas to determine the therapeutic potential of ICB and the significance of immune markers.

Methods

The expressions of PD-L1 and T cell markers (CD3, CD8, and FOXP3) were visualized by immunohistochemistry in 21 tissue samples of odontogenic carcinomas. Tumoral PD-L1 expression and the density and spatial distribution of T cell subsets were evaluated, from which TIME was determined. The associations of the variables with clinicopathological and prognostic factors were statistically analyzed.

Results

PD-L1 was positively expressed in 52.4% (11/21) of the cases studied. Among tumor types, ameloblastic carcinoma showed significantly higher PD-L1 expression (p = 0.016). TIME based on the intratumoral and stromal T cell distribution was immune-inflamed in 61.9% (13/21) and immune-excluded in 38.1% (8/21), with no immune-desert cases. PD-L1 expression was associated with the densities of all intratumoral T cell subsets (p = 0.03 for CD3, p = 0.03 for CD8, and p = 0.008 for FOXP3) but not with those of stromal T cells. High PD-L1 expression was associated with larger tumor size (p = 0.021), while the intratumoral CD8/CD3 ratio was inversely correlated with tumor size (p = 0.048).

Conclusion

These findings indicate the involvement of adaptive immune resistance in a subset of odontogenic carcinomas and support the therapeutic potential of ICB in patients with these rare malignancies.

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牙源性癌的肿瘤免疫微环境：评估免疫检查点阻断的治疗潜力。

背景：尽管免疫检查点阻断疗法（ICB）在各种癌症类型中的应用取得了最新进展，但其在牙源性癌中的疗效仍有待探索。本研究旨在调查牙源性癌中PD-L1的表达和肿瘤免疫微环境（TIME），以确定ICB的治疗潜力和免疫标记物的重要性：方法：采用免疫组化方法观察21个牙源性癌组织样本中PD-L1和T细胞标记物（CD3、CD8和FOXP3）的表达。评估了肿瘤 PD-L1 的表达以及 T 细胞亚群的密度和空间分布，并由此确定了 TIME。统计分析了这些变量与临床病理和预后因素的关系：结果：52.4%（11/21）的研究病例中 PD-L1 呈阳性表达。在肿瘤类型中，骨髓癌的PD-L1表达量明显更高（p = 0.016）。根据瘤内和基质 T 细胞分布，61.9%（13/21）的 TIME 为免疫炎症型，38.1%（8/21）为免疫排斥型，无免疫惰性病例。PD-L1 表达与所有瘤内 T 细胞亚群的密度相关（CD3 的 p = 0.03，CD8 的 p = 0.03，FOXP3 的 p = 0.008），但与基质 T 细胞的密度无关。PD-L1的高表达与肿瘤大小有关（p = 0.021），而瘤内CD8/CD3比值与肿瘤大小成反比（p = 0.048）：这些研究结果表明，适应性免疫抵抗参与了一部分牙源性癌的治疗，并支持 ICB 对这类罕见恶性肿瘤患者的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Oral Pathology & Medicine 医学-病理学

CiteScore

5.90

自引率

6.10%

发文量

121

审稿时长

4-8 weeks

期刊介绍： The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.