Abstract
Simple SummaryOur immune reaction depends on some ‘immune checkpoints’, such as PD-1, PD-L1 and CTLA4, that maintain homeostasis and define new pathways in the fight against carcinogenesis. Viral infections, including EBV (Epstein-Barr Virus) are one of the risk factors for laryngeal cancer. The aim of our study was to evaluate the level of PD-1 receptor in blood, tumor and lymph node samples collected from 45 laryngeal cancer patients and 20 healthy volunteers from control group. We detected the presence of EBV molecules in cancer samples and show the relationship between tumor progression and the level of PD-1 receptor. We confirmed, that EBV infection may affect the PD-1/PD-L1 pathway and develop the laryngeal cancer. What is important, the level of PD-1 on CD4+ T cells in lymph nodes increased the risk of death, so it can be an important prognostic factor (marker) for laryngeal cancer patients’ treatment and their prognosis.Due to the development of molecular diagnostic techniques, the latest research in the diagnosis of cancer diseases, including laryngeal cancer, has been focused on the occurrence of specific types of molecular patterns, including markers expressed on cells of the immune system (e.g., PD-1, PD-L1, and CTLA-4), which may be directly or indirectly involved in the development of neoplastic diseases. Laryngeal cancer is one of the diseases that is diagnosed more often in men than in women, and many factors are involved in its development, including environmental and lifestyle factors, viral infections (e.g., HPV, HHV-1, and EBV), and disorders of the immune system. In this study, we determined the level of PD-1 receptor expression on T and B lymphocytes and their relationships based on the classification of the grade and TNM scale, in turn based on blood, tumor, and lymph node samples from patients diagnosed with laryngeal cancer. In addition, we determined the presence of EBV genetic material in the tested biological materials as well as the degree of cancer advancement and its correlation with the level of PD-1 receptor expression. The results suggested that the level of PD-1 expression on T and B lymphocytes was significantly higher in the tumor samples as compared to the lymph node samples, and their comparison with the immunophenotype results from the blood samples provided statistically significant data on changes in the incidence of individual subpopulations of T and B lymphocytes and the level of PD-1 receptor expression. The analysis of the individual parameters of the TNM scale also showed significant changes between the PD-1 expression and the tested biological material in individual subgroups of the scale. We also found that the expression of PD-1 on the CD4+ T cells from the lymph node samples caused an almost 1.5-fold increase in the risk of death. In the analyses of the presence of EBV, the highest concentration was recorded in the tumor samples, then for the lymph node samples, and followed by the blood samples. Furthermore, we showed that the presence of EBV genetic material was positively correlated with the level of PD-1 expression in the tested biological materials.
Highlights
From year to year, we observe an increase in the number of people diagnosed with cancer of various origins and stages
In our analyses, we showed that the level of PD-1 expression on T and B lymphocytes was significantly higher in the tumor samples as compared to the lymph node samples for the CD19+ B, CD8+ T, and CD4+ T cells, and the level of PD-1 expression on T and B cells was significantly higher in the tumor samples than in the blood samples
We found that the PD-1 expression on CD4+ T cells from lymph node samples was associated with a 1.5-fold increased risk of death among patients diagnosed with laryngeal cancer
Summary
We observe an increase in the number of people diagnosed with cancer of various origins and stages. People diagnosed with laryngeal cancer are not among the world’s top cancers in terms of the number of new cases detected (according to the World Health Organization (WHO) in 2020, it was in the 20th position), it is important to understand this disease and its risks to the population. Statistical data compiled by WHO showed that in 2020, 184,615 new cases of laryngeal cancer were diagnosed worldwide, and over 21% of those were in Europe. 87.68% were men, and only 12.32% were women, which shows a clear prevalence in one sex This applied to the number of deaths, where data showed that in 2020, 19,604 people in Europe died of laryngeal cancer (which accounted for 19.63% of all deaths in the world), 89.87% of whom were men [1]. The molecular patterns detected in the development of head and neck cancers, including laryngeal cancer, include molecules such as epidermal growth factor receptor (EGFR) [2,3,4] telomerase activity [5], overexpression and amplification of cyclin D1 genes (CCND1) [6], cathepsin
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