Identifying potential immuno-oncology targets in salivary gland mucoepidermoid carcinoma based on inflammatory status and treatment response

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Oral Pathology & Medicine Pub Date : 2023-09-27 DOI:10.1111/jop.13488

Santhosh Kumar J. Urumarudappa, Vy Ngoc Thuy Tran, Hay Mar Oo, Monthira Suntiparpluacha, Somponnat Sampattavanich, Vinicius Rosa, Komkrit Ruangritchankul, Joao N. Ferreira, Risa Chaisuparat

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Abstract

Background

Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies.

Methods

A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively.

Results

Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders.

Conclusion

This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.

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根据炎症状态和治疗反应确定唾液腺粘液表皮样癌的潜在免疫肿瘤学靶点。

背景：粘液表皮样癌是一种罕见的涎腺恶性肿瘤。本研究旨在通过鉴定潜在的蛋白转录组生物标志物来研究粘液表皮样癌的炎症和免疫特征，以开发精确的免疫肿瘤学治疗策略。方法：在H&E染色后，对2013年至2022年间从诊断为粘液表皮样癌的患者中获得的30份活检进行分析，用QuPath对组织学炎症基质亚型和炎症热点进行评分。多重免疫荧光染色和NanoString nCounter PanCancer IO 360™ panel分别通过蛋白质组学和转录组学评估肿瘤微环境中高级别黏液表皮样癌病例的基质和肿瘤炎症特征。结果：与组织学炎症基质免疫沙漠（HIS-ID/冷）相比，组织学炎症间质炎症（HIS-INF/热）肿瘤邻域内的炎症细胞更大（p = 0.001）。在基质邻域中，治疗无应答者和应答者之间观察到相似的趋势（p = 0.0625）和基质中与炎症热点的界面（p = 0.0081），表明热肿瘤和无应答者的炎症反应增强。此外，应答者和非应答者之间泛免疫白细胞标志物CD45的表达存在显著差异，尤其是在肿瘤邻近区（p = 0.0341），但这对于PD-1和巨噬细胞组分来说并不健壮。此外，转录组学分析揭示了应答者和非应答者白细胞活化谱的关键差异。结论：本初步报告揭示了评估免疫白细胞组分和途径对粘液表皮样癌未来预后生物标志物发现的重要性，因为CD45驱动的炎症和免疫介质在高级别中的参与粘液表皮样癌治疗无效。这些发现可能有助于开发新的个性化免疫疗法。

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.