Introduction: Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis. However, whether CSCs also affect the immune system is not fully understood. We investigated correlations between the PD-L1+ CSCs, changes in T-cell phenotype in metastatic and non-metastatic lymph nodes (LNs) and response to treatment. Methods: LNs’ aspirates were obtained during the EBUS/TBNA procedure of 20 NSCLC patients at different stages of the disease. CSCs and T-cell characteristics were determined by flow cytometry. Results: PD-L1+ CSCs positively correlated with the percentage of Tregs, PD-1+ CD4 T cells and Tim3+ CD4+ T cells, whereas PD-L1+ CSCs were negatively correlated with CD4+ T cells and CD28+ CD4+ T cells. The percentage of PD-L1+ CSCs was higher in patients with progressive disease (PD) as compared to patients with stable disease (SD) or partial response (PR). Among T cells, only PD-1+ CD4+ T cells and Tim3+ CD4+ T-cell frequencies were higher in patients with PD as compared to patients with SD or PR. Conclusion: The frequency of PD-L1+ CSCs associates with an altered T-cell frequency and phenotype indicating that CSCs can affect the immune system. The higher percentage of PD-L1+ CSCs in patients with PD may confirm their resistance to conventional therapy, suggesting that CSCs may be an interesting target for immunotherapy.
Lung cancer remains one of the most aggressive solid tumors with an overall poor prognosis. Molecular studies carried out on lung tumors during treatment have shown the phenomenon of clonal evolution, thereby promoting the occurrence of a temporal heterogeneity of the tumor. Therefore, the biology of lung cancer is interesting. Cancer stem cells (CSCs) are involved in tumor initiation and metastasis. Aging is still the most important risk factor for lung cancer development. Spontaneously occurring mutations accumulate in normal stem cells or/and progenitor cells by human life resulting in the formation of CSCs. Deepening knowledge of these complex processes and improving early recognition and markers of predictive value are of utmost importance. In this paper, we discuss the CSC hypothesis with an emphasis on age-related changes that initiate carcinogenesis. We analyze the current literature in the field, describe our own experience in CSC investigation and discuss the technical challenges with special emphasis on liquid biopsy.
(1) The cells from the monocyte line play an important role as regulators of cancer development and progression. Monocytes present pro- and anti-tumor immunity and differentiation into macrophages. Macrophages are predominant in the lung cancer environment and could be evaluated by bronchoalveolar lavage fluid (BALF). (2) The aim of the study was analysis of monocytes: classical, intermediate and non-classical with expression of: CD62L, CD11c, CD18, HLA-DR in non-small cell lung cancer (NSCLC) and their correlation with BALF macrophages from lungs with cancer (clBALF) and healthy lungs (hlBALF). (3) A total of 24 patients with NSCLC and 20 healthy donors were investigated. Monocyte subtyping and macrophage counts were performed by flow cytometry. (4) There are three types in peripheral blood (PB): classical monocytes (CD14++CD16-), intermediate (CD14+CD16+) and non-classical (CD14-/+CD16++). We noticed a higher proportion of classical and intermediate monocytes in lung cancer than in healthy donors (76.2 vs. 67.3, and 7.9 vs. 5.2 p < 0.05). We observed a higher proportion of macrophages in clBALF then in hlBALF. A higher CD62L expression on all monocyte subtypes in healthy donors than in study group was found. There were positive correlations between: classical CD11c+, intermediate CD11c+, intermediate HLA-DR+ monocytes in PB with macrophages in clBALF. We did not observe these correlations with macrophages from hlBALF. (5) A predominance of classical and intermediate monocytes in lung cancer and the correlation between intermediate monocytes with CD11c+ and HLA-DR+ and macrophages from the NSCLC milieu support a role of monocyte-line cells in cancer immunity. A high proportion of monocytes with low expression of CD62L indicates the participation of monocytes in attenuation of anticancer response.
Studying the dynamics changes of neutrophils during innate immune response in coronavirus 2019 (COVID-19) can help understand the pathogenesis of this disease. The aim of the study was to assess the usefulness of new neutrophil activation parameters: Immature Granulocyte (IG), Neutrophil Reactivity Intensity (NEUT-RI), Neutrophil Granularity Intensity (NEUT-GI), and data relating to granularity, activity, and neutrophil volume (NE-WX, NE-WY, NE-WZ) available in hematology analyzers to distinguish convalescent patients from patients with active SARS-CoV-2 infection and healthy controls (HC). The study group consisted of 79 patients with a confirmed positive RT-PCR test for SARS-CoV2 infection, 71 convalescent patients, and 20 HC. We observed leukopenia with neutrophilia in patients with active infection compared to convalescents and HC. The IG median absolute count was higher in convalescent patients than in COVID-19 and HC (respectively, 0.08 vs. 0.03 vs. 0.02, p < 0.0001). The value of the NEUT-RI parameter was the highest in HC and the lowest in convalescents (48.3 vs. 43.7, p < 0.0001). We observed the highest proportion of NE-WX, NE-WY, and NE-WZ parameters in HC, without differences between the COVID-19 and convalescent groups. New neutrophil parameters can be useful tools to assess neutrophils’ activity and functionalities in the immune response during infection and recovery from COVID-19 disease.
3 August 2015 in Central European Journal of Immunology
Background: Paediatric respiratory tract infections are among the most common reasons for preschool and school absences and visits to physicians. The disease mainly involves the upper respiratory tract and is associated with fever, cough, sore throat, and running nose. Children with recurrent respiratory infections (RRI), which are defined as more than six serious diseases a year, are a difficult diagnostic challenge. The aim of this study was to assess immunological deviations in laboratory tests performed in children with RRI. Material and methods: In the retrospective study 25 children suffering from recurrent respiratory tract infection, aged 4.1 ±2.3 years, 13 boys and 12 girls, were involved. For all children chemiluminescence of granulocytes and immunophenotyping of lymphocytes from peripheral blood were examined. An immunophenotype of peripheral blood lymphocytes involved evaluation of T cell, B cells, and NK cells, examined with flow cytometry. Results: Eleven of the studied children had decreased chemiluminescent response to stimulants, normal response was found for nine children, and five children had an increased result of the test. Five of the 25 children had decreased B cells number, and five had decreased number of T cells including decrease of CD4, as well as CD8 positive cells. Children with decreased chemiluminescence had more frequent neutropaenia than children with normal or increased chemiluminescent response, p < 0.05 (exact Fisher test). Conclusions: Recurrent respiratory tract infection could be associated with improper neutrophils response to pathogens, and immunological examination should be performed to find the reason for the increased number of infections in a year.