Expression of PD-1/PD-L1 and Inflammasome Mediators in Oral Squamous Cell Carcinoma: Correlation with Key Clinical and Pathological Variables

Authors

DOI:

https://doi.org/10.20883/medical.e1446

Keywords:

oral squamous cell carcinoma (OSCC), histopathology, PD-1/PD-L1, NLRP3 inflammasome, NAIP/NLRC4 inflammasome, clinical variables

Abstract

Objective. Oral squamous cell carcinoma (OSCC) is a leading cause of head and neck cancer morbidity and mortality. This study aimed to explore the relationship between immune checkpoint regulation and inflammasome-related pathways in OSCC, focusing on the Programmed cell death protein 1 (PD-1)/ Programmed cell death ligand 1 (PD-L1) axis and components of the NLR family pyrin domain containing 3 (NLRP3 and NLR family apoptosis inhibitory protein (NAIP) inflammasomes in relation to relevant clinical variables. 
Design. This retrospective observational study included 30 patients with OSCC who underwent surgical resection. Histopathological expression of PD-1, PD-L1, NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC/PYCARD), caspase-1, Interleukin-1 beta (IL-1β), IL-18, caspase-5, caspase-8, and NAIP was assessed by immunohistochemistry using ordinal scoring. Associations with clinical features were evaluated using non-parametric tests and Spearman correlation analyses. Inter-marker relationships were explored using correlograms and heatmaps, with stratification by tumour grade. Exploratory binary logistic regression models were applied to examine associations between marker expression and selected clinical variables.
Results. Marker expression showed significant associations with tumour grade, relapse, vascular invasion, and oral hygiene, whereas age, sex, smoking status, alcohol consumption, and other clinicopathological variables were not significantly related. Higher-grade tumours exhibited stronger and more extensive inter-marker correlations, suggesting coordinated activation of immune and inflammatory pathways. Increased expression of PD-L1, NAIP, NLRP3, caspase-1, caspase-5, and PYCARD was associated with higher tumour grade, while relapse was linked to elevated expression of NAIP, NLRP3, caspase-1, and IL-18. Poor oral hygiene was inversely associated with the expression of multiple immune and inflammasome-related markers, whereas vascular invasion correlated with broadly increased marker expression. 
Conclusions. These findings indicate that immune checkpoint signalling and inflammasome-related pathways are closely associated with aggressive clinicopathological features in OSCC. The coordinated expression patterns observed support a role for inflammation-driven immune modulation in disease progression. Although exploratory, this study provides a framework for future investigations aimed at validating these pathways as biomarkers or therapeutic targets in larger cohorts.

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Author Biographies

  • Oscar Fraile-Martinez, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Cielo Garcia-Montero, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • María Jesus Garrido-Gil, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Laura Ríos-Espinosa, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Diego Liviu Boaru, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Diego De Leon-Oliva, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Patricia De Castro-Martinez, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

  • Claude Pereda-Cerquella, University of Alcalá

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain

  • Majd N. Michael Alhaddadin, University of Alcalá

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain

  • Silvestra Barrena-Blázquez, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain

  • Antonio Rios-Parra, University of Alcalá

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain

  • Laura Lopez-Gonzalez, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

    Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • Luis G . Guijarro, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

    Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of Systems Biology, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • Alejandro Coca, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain

  • Víctor Roberto Baena Romero, University of Alcalá

    Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain.

  • Carlos Daniel Padilla Ansala, University of Alcalá

    Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain

  • María del Mar Royuela García, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Biomedicine and Biotechnology, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • María del Val Toledo Lobo, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Biomedicine and Biotechnology, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • Leonel Pekarek, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario de Guadalajara

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain.

  • Montserrat Chao Crecente, University of Alcalá

    Pathological Anatomy Service of the “Severo Ochoa” University Hospital in Leganés.

  • Ángel Asúnsolo, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • Melchor Alvarez-Mon, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Príncipe de Asturias

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, 28806 Alcala de Henares, Spain.

  • Julio Acero, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá, Hospital Universitario Ramón y Cajal

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
    Department of Oral and Maxillofacial Surgery, Ramon y Cajal University Hospital, 28034 Madrid, Spain.

  • Raúl Díaz-Pedrero, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá, Hospital Universitario del Henares

    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of Systems Biology, University of Alcalá, 28801 Alcalá de Henares, Spain.
    Department of General and Digestive Surgery, Príncipe de Asturias, University Hospital, 28805 Alcala de Henares, Spain.

  • Miguel A. Saez, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
    Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.

  • Miguel A. Ortega, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria

    Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, Network Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), University of Alcalá, 28801 Alcalá de Henares, Spain.
    Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

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Expression of PD-1/PD-L1 and Inflammasome Mediators in Oral Squamous Cell Carcinoma: Correlation with Key Clinical and Pathological Variables. JMS [Internet]. 2026 Mar. 31 [cited 2026 May 16];95(1):e1446. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/1446