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

Autor: Urumarudappa SKJ; Avatar Biotechnologies for Oral Health and Healthy Longevity, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand., Tran VNT; Oral Biology, International Graduate Program, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand., Oo HM; Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Suntiparpluacha M; Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Sampattavanich S; Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Rosa V; Faculty of Dentistry, National University of Singapore, Singapore, Singapore.; Oral Care Health Innovations and Designs Singapore, National University of Singapore, Singapore, Singapore., Ruangritchankul K; Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Ferreira JN; Avatar Biotechnologies for Oral Health and Healthy Longevity, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand., Chaisuparat R; Avatar Biotechnologies for Oral Health and Healthy Longevity, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.; Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology [J Oral Pathol Med] 2023 Nov; Vol. 52 (10), pp. 939-950. Date of Electronic Publication: 2023 Sep 27.
DOI: 10.1111/jop.13488
Abstrakt: 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.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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