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Abstract Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. Aim To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients. Material and methods The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years). In all subjects lung function tests and HRCT scanning of the chest were performed. External (D) and internal (L) diameters of the airways were assessed at five selected lung levels. The lumen area (AL), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). Total and differential cell counts were assessed in the BAL fluid. Results Mean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS). No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS). Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P < 0.05) and lumen area (r = -0.7, P < 0.05) were found in asthmatics. There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients. Conclusions In mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid.

Abstract Background Exposure to inhaled endotoxins (lipopolysaccharides, LPS) of Gram-negative bacteria commonly found in indoor environments and assessed in secondary tobacco smoke, has been associated with airway inflammation and asthma exacerbation. The bronchoalveolar lavage fluid (BALf) from patients with interstitial lung diseases (sarcoidosis, lung fibrosis, smoking-related ILD, eosinophilic disorders) was analyzed for the markers of lipopolysaccharide (LPS, endotoxin). Methods BALf was obtained from patients with diffuse lung diseases: idiopathic pulmonary fibrosis (n = 42), sarcoidosis (n = 22), smoking-related-ILD (n = 11) and eosinophilic disorders (n = 8). Total cell count and differential cell count were performed. In addition, samples were analyzed for 3-hydroxy fatty acids (3-OHFAs) of 10–18 carbon chain lengths, as markers of LPS, by gas chromatography-tandem mass spectrometry. Results The highest LPS concentration was found in patients with eosinophilic disorders and the lowest in patients with sarcoidosis (p< 0.05) followed by the lung fibrosis and the sr-ILD patients. The difference between LPS in BALf with extremely high eosinophil proportion (> 25%) and those with lower proportion was also significant (p = 0.014). A significant correlation was found between LPS and eosinophils, but not between LPS and lymphocytes, neutrophils, or macrophages count. Conclusions A positive relationship of LPS and eosinophilic pulmonary disorders may be linked to a persistent eosinophil activation mediated by Th2 pathway: chronic endotoxin exposure would intensify Th2 pathway resulting in fibrosis and, at the same time, eosinophil stimulation, and hence in eosinophilic pulmonary disorders.

The progress in lung cancer treatment is closely interlinked with the progress in diagnostic methods. There are four steps before commencing lung cancer treatment: estimation of the patient's performance status, assessment of disease stage (tumour, node, metastasis), recognition of histological subtype, and detection of biomarkers. The resection rate in lung cancer is <30% and >70% of patients need systemic therapy, which is individually adjusted. Accurate histological diagnosis is very important and it is the basis of further molecular diagnosis. In many cases only small biopsy samples are available and the rules for their assessment are defined in this review. The use of immunochemistry with at least thyroid transcription factor 1 (TTF1) and p40 is decisive in distinction between lung adenocarcinoma and squamous cell carcinoma. Molecular diagnosis and detection of known driver mutations is necessary for introducing targeted therapy and use of multiplex gene panel assays using next-generation sequencing is recommended. Immunotherapy with checkpoint inhibitors is the second promising method of systemic therapy with best results in tumours with high programmed death-ligand 1 (PD-L1) expression on cancer cells. Finally, the determination of a full tumour pattern will be possible using artificial intelligence in the near future., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©ERS 2024.)

(1) Background: There is a difference in the course of lung cancer between women and men. Therefore, there is a need to evaluate various factors in the patient population treated in daily practice. The purpose of this study was to analyze the clinical, sociodemographic and psychological aspects of female lung cancer. To better express the results, we compared women and men. (2) Methods : Consecutive patients with a history of lung cancer treatment admitted to the outpatient oncology clinic (Department of Lung Cancer and Chest Tumours, Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw) and the Department of Internal Medicine, Pulmonary Diseases and Allergy, were enrolled. We conducted analyses of the clinical, psychological and socioeconomic factors of women with lung cancer treated in everyday practice, including a comparison with a group of men. Demographic data were collected from a self-administered questionnaire. We used the Perceived Stress Scale (PSS-10) and Acceptance of Illness Scale (AIS) questionnaires for psychological evaluation. (3) Results : A total of 100 patients with confirmed primary lung cancer with a history of treatment were enrolled in the study (50 women and 50 men). We found a significantly shorter history of smoking in the group of women; at the same time, there were no differences in the reported incidence of COPD. Despite comparable results to men on the psychological questionnaire (PSS-10, AIS), women more often reported a willingness to be supported by a psychologist or psychiatrist due to lung cancer. However, they did not decide to consult them more often than men. Immunotherapy was a significantly less frequently used method in women. (4) Conclusions : We should be more active in finding out the willingness to consult a psychologist or psychiatrist among women with lung cancer. The diagnosis of COPD should be considered more often among women due to the lack of differences in the reported incidence of COPD between men and women, despite a clear contrast in the number of pack-years.

Macrophages play an important role in the suppression and activation of immune anti-cancer response, but little is known about dominant macrophage phenotype in the lung cancer environment, evaluated by bronchoalveolar lavage fluid (BALF). The aim of this study was to characterize macrophages in BALF from a lung affected by cancer (cBALF) and a healthy lung (hBALF) of the same patient regarding their individual macrophage polarization and selected cytokines profile. A total of 36 patients with confirmed lung cancer were investigated. Macrophages markers: CD206 CD163 CD80 CD86 CD40 CD45, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1β, IL-12, IL-23, and TGF-β) profile was analyzed. There was higher median proportion of macrophages in Cbalf than in Hbalf. The population of macrophages presented immunophenotype: Ccd68+ bright CD206+ bright CD163+ bright CD80+ CD86+ CD40+ bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. The highest concentrations of IL-1RA and IL-6 were in Cbalf and Hbalf supernatant. There were the correlations between pro- and anti-inflammatory cytokines. The findings showed that macrophages include a diverse and plastic group with the presence of different antigens and cytokines, and determining the target phenotype is a complex and variable process.

Introduction: More information is needed on gender differences in lung cancer surgery. Thus, we conducted a retrospective study on thoracic treatment of non-small cell lung cancer (NSCLC) patients between 2007 and 2020 in Poland. The aim was to characterize sex differences in survival after complete surgical resection and to compare postoperative complications between Polish men and women. The main aspects that were compared between women and men were as follows: type of surgery and postoperative staging, morbidity and mortality, thoracic surgery complications, comorbidities, and overall survival based on a univariate analysis including propensity score matching (PSM) and a multivariate analysis., Materials and Methods: Data were collected retrospectively from the Polish Lung Cancer Study Group database. Patients who were surgically treated for NSCLC between 2007 and 2020 (n = 17,192) were included in the study., Results: The univariate analysis showed significantly better survival in women than in men. Women had better 5-year survival compared to men both for adenocarcinoma and squamous cell carcinoma (66% vs. 53%, p < 0.0001 and 65% vs. 51%, p<0.0001%, respectively), for both smokers and non-smokers (65% vs. 52%, p < 0.0001 and 65% vs. 51%, p < 0.0001, respectively), all age groups, and all stages (IA1 to III B). In the PSM analysis, statistically significant differences in favor of women were found for lower lobectomy (67% vs. 50%, p < 0.0001) and upper lobectomy (67% vs. 56%, p < 0.0001). Overall, postoperative complications occurred in 33.1% of patients and were observed more often in men than in women (35.8% vs. 28.6%, p < 0.001)., Conclusions: Women with NSCLC who were treated surgically had a better long-term outcome compared to men, with no significant difference in disease severity. In addition to gender, the histological type, comorbidities, and type of surgery and surgical approach are also important., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Significance: The success rate of hematopoietic stem cell transplantation depends mainly on the number of transplanted hematopoietic stem/progenitor cells (HSPCs) followed by the speed of their engraftment in the myeloablated transplant recipient. Therefore, clinical outcomes will significantly benefit from accelerating the homing and engraftment of these cells. This is, in particular, important when the number of cells available for the transplantation of HSPCs is limited. Recent Advances: We postulated that myeloablative conditioning for hematopoietic transplantation by radio- or chemotherapy induces a state of sterile inflammation in transplant recipient peripheral blood (PB) and bone marrow (BM). This state is mediated by activation of the BM stromal and innate immunity cells that survive myeloablative conditioning and respond to danger-associated molecular patterns released from the cells damaged by myeloablative conditioning. As a result of this, several factors are released that promote proper navigation of HSPCs infused into PB of transplant recipient and prime recipient BM to receive transplanted cells. Critical Issues: We will present data that cellular innate immunity arm and soluble arm comprised complement cascade proteins, promoting the induction of the BM sterile inflammation state that facilitates the navigation, homing, and engraftment of HSPCs. Future Directions: Deciphering these mechanisms would allow us to better understand the mechanisms that govern hematopoietic recovery after transplantation and, in parallel, provide important information on how to optimize this process in the clinic by employing small molecular modifiers of innate immunity and purinergic signaling. Antioxid. Redox Signal. 37, 1254-1265.

Background: Non-small cell lung cancer diagnosed in young patients is rare. Younger patients with lung cancer are mostly female and have a more advanced stage at initial diagnosis. To our knowledge, no studies have compared single-surgical treatment in different age groups among women. Our study aimed to elucidate the clinicopathological characteristics and the best strategies for surgically treating young women with non-small-cell lung cancer., Methods: The data were collected retrospectively from the Polish Lung Cancer Study Group database. Women who were surgically treated for non-small-cell lung cancer between 2007 and 2020 were included in the study. The participants (n=11,460) were divided into two subgroups: aged ≤55 and >55 years., Results: Statistically significant differences were found for grades IB, IIA, IIIA, and IIIB (22.8% vs. 24.5%, 5.3% vs. 7.5%, 19.3% vs. 15.8%, 5.8% vs. 3.2%, for younger and older women, respectively, all P<0.001). The univariate analysis showed a higher percentage of 5-year survival in the group of younger women than in older women (0.67 vs. 0.64, P=0.00076). Regarding the stage of advancement, statistically significant differences in survival were found for stages IA1, IA2, and IIIA (0.95 vs. 0.86, P=0.047; 0.88 vs. 0.79, P=0.003; 0.5 vs. 0.42, for younger and older women, respectively, all P=0.01). Postoperative complications were more common in older than younger women (27.6% vs. 23.1%, P<0.001). However, there were no statistically significant differences in the number of hospitalization days since surgery and postoperative 30-day mortality., Conclusions: Younger women treated surgically were characterized by a lower percentage of comorbidities, were treated in a more advanced stage of the disease and had a lower percentage of postoperative complications, which, however, did not affect the hospitalization time. Despite the more advanced stage of the disease, survival in selected stages was much better than in the group of older women., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-443/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Dendritic cells (DCs) play a pivotal role in the homeostasis of the immune system. The tumor microenvironment impairs the proper function of DCs. The immunomodulatory properties of DCs in lung cancer are of interest. In the present study, we analysed DCs subsets and immune cells with the expression of immunomodulatory molecules: PD-1 and PD-L1 and co-stimulatory molecule CD80 in metastatic, non-metastatic lymph nodes (LNs) and peripheral blood (PB). LNs aspirates were obtained during the EBUS/TBNA procedure of 29 patients with primary lung cancer. The cells were analyzed by flow cytometry. We reported a higher percentage of DCs in the metastatic than in the non-metastatic LNs and the PB (0.709% vs. 0.166% vs. 0.043%, p < 0.0001). The proportions of PD-1 + , PD-L1 + and CD80 + DCs were higher in the metastatic LNs than in the non-metastatic ones. A higher proportion of regulatory DCs (DCregs) was found in the metastatic ones than in the non-metastatic LNs (22.5% vs. 3.1%, p = 0.0189). We report that DCs cells show increased expression of PD-1, PD-L1 and CD80 molecules that can interact with T lymphocytes. It can be assumed that mature DCs infiltrating metastatic LNs can develop into DCregs, which are involved in the suppression of anti-tumor response., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tobacco smoking remains the main cause of tobacco-dependent diseases like lung cancer, chronic obstructive pulmonary disease (COPD), in addition to cardiovascular diseases and other cancers. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. A patient with COPD has a four- to six-fold greater risk of developing lung cancer independent of smoking exposure, when compared to matched smokers with normal lung function. The 10 year risk is about 8.8% in the COPD group and only 2% in patients with normal lung function. COPD is not a uniform disorder: there are different phenotypes. One of them is manifested by the prevalence of emphysema and this is complicated by malignant processes most often. Here, we present and discuss the clinical problems of COPD in patients with lung cancer and against lung cancer in the course of COPD. There are common pathological pathways in both diseases. These are inflammation with participation of macrophages and neutrophils and proteases. It is known that anticancer immune regulation is distorted towards immunosuppression, while in COPD the elements of autoimmunity are described. Cytotoxic T cells, lymphocytes B and regulatory T cells with the important role of check point molecules are involved in both processes. A growing number of lung cancer patients are treated with immune check point inhibitors (ICIs), and it was found that COPD patients may have benefits from this treatment. Altogether, the data point to the necessity for deeper analysis and intensive research studies to limit the burden of these serious diseases by prevention and by elaboration of specific therapeutic options.

Lymphocytes play a leading role in regulation of the immune system in lung cancer patients. The recognition of T cells profile may help in prediction of effectiveness of anticancer immunotherapy. The aim of the study was to determine the dominant subpopulation of CD4+ and CD8+ lymphocytes in metastatic and non-metastatic lymph nodes (LNs) of lung cancer patients. LNs aspirates were obtained during EBUS/TBNA procedure and cells were analyzed by flow cytometry. We showed a higher percentage of CD4+ and CD8+ effector memory T cells in the metastatic than in the non-metastatic LNs (28.6 vs. 15.3% and 28.6 vs. 14.0%, p< 0.05). The proportion of CD45RO+ T regulatory cells (CD45RO+ Tregs) was higher in the metastatic LNs than in the non-metastatic ones (65.6 vs. 31%, p< 0.05). We reported the significant differences in T cell subsets depending on the lung cancer metastatic process. We observed that the effector memory T cells were predominant subpopulations in metastatic LNs. Lymphocyte profile in LNs is easy to evaluate by flow cytometry of EBUS/TBNA samples and may reflect the immune status in lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kwiecień, Rutkowska, Sokołowski, Bednarek, Raniszewska, Jahnz-Różyk, Rzepecki and Domagała-Kulawik.)

Sex hormones are included in many physiological and pathological pathways. Estrogens belong to steroid hormones active in female sex. Estradiol (E2) is the strongest female sex hormone and, with its receptors, contributes to oncogenesis, cancer progression and response to treatment. In recent years, a role of immunosurveillance and suppression of immune response in malignancy has been well defined, forming the basis for cancer immunotherapy. The interplay of sex hormones with cancer immunity, as well as the response to immune checkpoint inhibitors, is of interest. In this review, we investigate the impact of sex hormones on natural immune response with respect to main active elements in anticancer immune surveillance: dendritic cells, macrophages, lymphocytes and checkpoint molecules. We describe the main sex-dependent tumors and the contribution of estrogen in their progression, response to treatment and especially modulation of anticancer immune response.

Different subpopulations of monocytes and dendritic cells (DCs) may have a key impact on the modulation of the immune response in malignancy. In this review, we summarize the monocyte and DCs heterogeneity and their function in the context of modulating the immune response in cancer. Subgroups of monocytes may play opposing roles in cancer, depending on the tumour growth and progression as well as the type of cancer. Monocytes can have pro-tumour and anti-tumour functions and can also differentiate into monocyte-derived DCs (moDCs). MoDCs have a similar antigen presentation ability as classical DCs, including cross-priming, a process by which DCs activate CD8 T-cells by cross-presenting exogenous antigens. DCs play a critical role in generating anti-tumour CD8 T-cell immunity. DCs have plastic characteristics and show distinct phenotypes depending on their mature state and depending on the influence of the tumour microenvironment. MoDCs and other DC subsets have been attracting increased interest owing to their possible beneficial effects in cancer immunotherapy. This review also highlights key strategies deploying specific DC subpopulations in combination with other therapies to enhance the anti-tumour response and summarizes the latest ongoing and completed clinical trials using DCs in lung cancer., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

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.

Background: The efficacy of immune checkpoint inhibitors (ICIs) remains unexpected and in some patients the resistance to anti-programmed death-1 (anti-PD-1) and anti-programmed death ligand 1 (anti-PD-L1) agents is observed. One of possible explanation may be PD-L2 activity. PD-1 ligands: PD-L1 and PD-L2 are present on cancer cells but also, not without significance, on alveolar macrophages (AMs) contributing to immune-suppression in the tumor microenvironment. The aim of this study was to analyse PD-L2, PD-L1 expression on AMs in bronchoalveolar lavage fluid (BALF) in relation to PD-1 positive T lymphocytes., Methods: Seventeen patients with lung cancer were investigated. BALF cells from the lung with cancer (clBALF) and from the opposite "healthy" lung (hlBALF) and peripheral blood (PB) lymphocytes were investigated. Flow cytometry method was used., Results: We found that 100% of CD68+ AMs from the clBALF were PD-L1 and PD-L2-positive. Unexpectedly, fluorescence minus one (FMO) PD-L1 and PD-L2 stained controls and isotype controls also showed strong autofluorescence. The hlBALF AMs exhibited a similar PD-L1 and PD-L2 autofluorescence. The median proportion of PD-1+ T lymphocytes was higher in the clBALF than the hlBALF and PB (28.9 vs. 23.4% vs. 15.6%, P=0.0281)., Conclusions: We discussed the opportunities of exploring the PD-1-PD-L1/PD-L2 pathway in the lung cancer environment, which may help to find new potential biomarkers for immunotherapy. We concluded that precise identification by flow cytometry of macrophages in the BALF is possible, but our study showed that the autofluorescence of macrophages did not allow to assess a real expression of PD-L2 as well as PD-L1 on AMs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1103). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Immunotherapy with immune checkpoint inhibitors (ICIs) was shown to improve survival of patients with solid tumors such as: melanoma, renal carcinoma, non-small cell lung cancer, cutaneous carcinomas, or head and neck carcinoma. However, a special type of ICIs toxicity is observed, namely noninfectious inflammation of different organs associated with autoimmunity known as immune‑related adverse events (irAEs). This noninfectious inflammation may affect the endocrine system, gastrointestinal tract, heart, skin, and nervous system. The lungs are also often involved and this condition is referred to as checkpoint inhibitor pneumonitis. The toxicity of ICIs is graded from 1 to 5 depending on the clinical course, 5 being a fatal complication. Corticosteroids are the treatment of choice, generally with good efficacy. In some difficult cases, escalation of immunosuppression is required. Knowledge of irAEs should be promoted among clinicians of all specialties, nurses, patients and their families. The aim of this review is to present the wide spectrum of irAEs: clinical signs and symptoms, differential diagnosis, diagnostic procedures, and treatment. Data are supported by our own clinical observations.

(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.

Over the past decade, immune checkpoint inhibitors have revolutionized the treatment of non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from PD-(L)1 blockade, yet, the PD-L1 tumor cell expression is the only approved biomarker, and other biomarkers have been investigated. In the present study, we analyzed the presence of immunomodulatory molecules: PD-L1, CD47, CD73, Fas, and FasL on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph nodes (LNs) aspirates and refer it to the lymphocyte subpopulation in peripheral blood (PB). PB samples and LNs aspirates obtained during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA) procedure of 20 patients at different stages of NSCLC. The cells were analyzed by multiparameter flow cytometry. We reported the higher frequency of MTCs and CSCs expressing the investigated immunomodulating molecules in metastatic LNs than in nonmetastatic. The expression of CD47 and PD-L1 was significantly higher on CSCs than on MTCs. Among the lymphocyte subpopulation in PB, we observed a higher frequency of PD-1+ CD8 T cells and Fas+ CD8 T cells in patients with confirmed metastases than in nonmetastatic. Next, we found that the percentage of FasL+ MTCs correlated with the frequency of Fas+ CD3 T cells in LNs aspirates and Fas+ CD8 T cells in PB. Finally, we found that patients with metastatic disease had a significantly higher FasL+/Fas+ MTCs ratio than patients with nonmetastatic disease. Both MTCs and CSCs express different immunomodulatory molecules on their surface. The frequency of FasL+ MTCs associates with altered distribution of Fas+ lymphocyte subpopulations in LNs and PB.

Purpose: Obstructive sleep apnea syndrome (OSAS) is associated with alterations in immune system which may lead to serious complications. The aim of this study was to explore lymphocyte populations in OSAS with special attention to the Fas-positive cells., Methods: Fifty-one patients with confirmed OSA and 20 healthy subjects were investigated. The OSA severity indices, data concerning comorbidities, and markers of inflammation and metabolic disorders were collected. Flow cytometry was used to analyze the lymphocyte profile and expression of Fas receptors (CD95). Concentration of adiponectin, IL-1β, TNF-α, and sFas were measured., Results: Proportions of Fas-positive cells in the pool of CD4+ and Fas-positive in the pool of CD8+ cells in the blood of patients were significantly increased when compared with healthy subjects (74.5% vs. 65.6% and 78.8% vs.70.9%, respectively, p < 0.05). No correlation with OSA severity was found. However, the proportion and number of Fas+ cells were elevated in obese patients, in non-smokers, and in patients suffering from COPD and hypertension. There were several significant relations of Fas+ cells with inflammatory markers of systemic inflammation., Conclusion: Lymphocytes with the expression of Fas receptor are associated with systemic inflammation in OSAS.

Introduction: M2 macrophages are predominant in the immune infiltrates of resected tumours, but little is known about macrophage phenotype in the local lung cancer environment, which may be evaluated by bronchoalveolar lavage fluid (BALF)., Aim of the Study: To find differences between BALF from lung affected by cancer (clBALF) and hlBALF from the opposite, healthy lung, as a control, from the same patient, regarding their individual macrophage polarization and their correlation with IL-10 and TGF-β., Material and Methods: Eighteen patients with confirmed lung cancer were investigated. Macrophage subtyping was performed by immunofluorescence with antibodies anti-CCR7 and CD163 (M1 and M2, respectively)., Results: We found five populations of macrophages: cells with a single reaction: only for CCR7+ or CD163+, a double reaction (CCR7+CD163+), cells with a stronger CD163 (CCR7 low CD163+), and cells with a stronger CCR7 (CCR7+CD163 low ). The main population in the clBALF was composed of cells with a phenotype similar to M2 (CCR7 low CD163+), while in the hlBALF the predominating phenotype was the one similar to M1 (CCR7+CD163 low ). The median proportion of TGF-β1 concentration was higher in the clBALF and hlBALF supernatant than in the serum., Conclusions: In this study we confirmed the usefulness of the immunofluorescence method with CCR7 and CD163 in the evaluation of BALF macrophage polarization in lung cancer., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Termedia.)

Immunotherapy with immune checkpoint inhibitors (ICIs) revolutionized therapy of solid tumors, among them- lung cancer. PD-1, PD-L1 blockers have been shown to improve overall survival in advanced, metastatic non-small cell lung cancer. In individual patients, 3-5-year survival has been achieved. Nivolumab, pembrolizumab, atezolizumab are approved in lung cancer treatment. Practical observations in reallife show that the results are comparable with those achieved in clinical trials. The effects of ICIs depend on the patient performance status; age, sex, histology; the presence of brain metastases have not modified treatment results. ICIs therapy is safe and well tolerated; immune related adverse events are observed. Pneumonitis may be a serious and fatal complication, but glucocorticoids are usually curative. For proper patients selection for ICIs treatment, the detection of PD-L1 expression on cancer cells is used. The so-called "hot" tumors with high expression of PD-L1 and abundant infiltration by cytotoxic cells seem to better respond to treatment than "cold" tumors.

Immunosuppressive activity of regulatory T and B cells is critical to limit autoimmunity, excessive inflammation, and pathological immune response to conventional antigens or allergens. Both types of regulatory cells are intensively investigated, however, their development and mechanisms of action are still not completely understood. Both T and B regulatory cells represent highly differentiated populations in terms of phenotypes and origin, however, they use similar mechanisms of action. The most investigated CD4 + CD25 + regulatory T cells are characterized by the expression of Foxp3 + transcription factor, which is not sufficient to maintain their lineage stability and suppressive function. Currently, it is considered that specific epigenetic changes are critical for defining regulatory T cell stability in the context of their suppressive function. It is not yet known if similar epigenetic regulation determines development, lineage stability, and function of regulatory B cells. Phenotype diversity, confirmed or hypothetical developmental pathways, multiple mechanisms of action, and role of epigenetic changes in these processes are the subject of this review.

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Regulation of immune response was found to play an important role in the course of many diseases such as autoimmune diseases, allergy, malignancy, organ transplantation. The studies on immune regulation focus on the role of regulatory cells (Tregs, Bregs, regulatory myeloid cells) in these disorders. The number and function of Tregs may serve as a marker of disease activity. As in allergy, the depletion of Tregs is observed and the results of allergen-specific immunotherapy could be measured by an increase in the population of IL-10 + regulatory cells. On the basis of the knowledge of anti-cancer immune response regulation, new directions in therapy of tumors are introduced. As the proportion of regulatory cells is increased in the course of neoplasm, the therapeutic action is directed at their inhibition. The depletion of Tregs may be also achieved by an anti-check-point blockade, anti-CD25 agents, and inhibition of regulatory cell recruitment to the tumor site by affecting chemokine pathways. However, the possible favorable role of Tregs in cancer development is considered and the plasticity of immune regulation should be taken into account. The new promising direction of the treatment based on regulatory cells is the prevention of transplant rejection. A different way of production and implementation of classic Tregs as well as other cell types such as double-negative cells, Bregs, CD4 + Tr1 cells are tested in ongoing trials. On the basis of the results of current studies, we could show in this review the significance of therapies based on regulatory cells in different disorders.

Background: Anxiety and panic attacks are more common in chronic obstructive pulmonary disease (COPD) than in the overall population. Individuals with panic attacks often attempt to avoid situations perceived as at risk of eliciting bodily sensations such as dyspnea, which paradoxically may lead to anxiety-related responsivity. Although there is some evidence that COPD individuals restrict their participation in various life activities because they fear that these may trigger breathlessness, little is known about agoraphobic avoidance and its impact on cognitions and emotional distress in this population. It was thus our aim to investigate the degree of agoraphobic avoidance in COPD individuals, its clinical concomitants and consequences., Methods: A total of 48 patients with COPD and 48 matched controlled subjects completed measures of anxiety sensitivity, agoraphobic avoidance, anxiety and depression. Objective COPD severity was measured using forced expiratory volume in the first second., Results: Patients showed significant impairment in respiratory functioning and psychological distress. Relative to the control, the COPD group exhibited greater depression, anxiety, physical symptom concerns and avoidance (alone and accompanied), irrespective of whether they were panickers or not. Patients with high avoidance showed more intense physical concerns when compared to those with low avoidance. Importantly, the level of avoidance predicted emotional distress and increased physical concerns in COPD., Conclusions: Physical concerns scores in COPD patients are partially explained by avoidance in this group. The results of the study provide evidence for the importance of evaluating avoidance in COPD patients and implicate targeting this behavior in therapeutic interventions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of the study was to compare the presence of regulatory T cells (Tregs) in the local lung cancer environment versus systemic immune response based on the examination of bronchoalveolar lavage fluid (BALf) and peripheral blood (PB) from the same patient. 35 patients with lung cancer were investigated. Flow cytometry method with panel of antibodies: anti CD4/CD25/FoxP3/CD127 for Tregs identification was used. We observed significantly higher proportion of Tregs in the BALF than in PB (median 9.4 vs. 5.4%, p<0.05). The increased proportion of Tregs in patients with advanced disease and in adenocarcinoma was found. This study confirmed the usefulness of BALF analysis in evaluation of immune response in lung cancer. Detection of Tregs in the local tumour environment may have therapeutic relevance in individual indication for anti-cancer immune-therapies., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The role of bronchoalveolar lavage fluid (BALf) examination in differential diagnosis of interstitial lung diseases (ILD) was established. Currently, functional polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) subpopulations is emphasized. The aim of our study was to compare the proportion of M1 and M2 in BALf of patients with different ILD. BALf samples were collected from 75 ILD patients: sarcoidosis (SA, 36), hypersensitivity pneumonitis (HP, 10), non-specific interstitial pneumonia (NSIP, 8), idiopathic pulmonary fibrosis (IPF, 6) and other ILD (15). Phenotyping was performed by immunocytochemistry with anti-CD40 and CD163 antibodies (for M1 and M2, respectively). For both, CD40 and CD163, three populations of cells have been specified: small cells with strong (+++), large cells with weak (+) and cells with no (-) reaction. Due to lack of statistically significant differences between patients with HP, NSIP and IPF, they were classified into a common group and compared to the group of patients with sarcoidosis. The median proportion of macrophage population was as follows: for CD40: 61%, 35%, 2% in patients with SA and 49%, 47%, 3% in patients with other ILD and for CD163: 55%, 35%, 5% in SA and 53%, 43%, 1% in ILD patients, respectively. We found a significantly higher proportion of M1 in SA when compared with other ILD. Our study showed no evidence of defined polarization of alveolar macrophages in different types of interstitial lung diseases. However, we emphasized the role of CD40 positive cells in sarcoidosis and the role of CD163 positive cells in fibrotic diffuse lung diseases.

Background: Obstructive sleep apnoea syndrome (OSAS) brings risk of serious complications. The study objective was to assess elements of the cellular immune response in the course of OSAS., Methods: Peripheral blood (PB) lymphocytes: T, B, NK, NKT-like, Th, Tc, and HLA DR+ T cells were evaluated by flow cytometry of 48 OSA patients; the concentration of adiponectin, interleukin 1β, and TNFα was measured by ELISA method. The OSA complication score was developed and used for statistical analysis., Results: The proportion of B cells and Th/Tc ratio were significantly lower in the BP of OSA patients when compared with control subjects (median 7.9 versus 10.9%, 0.9 versus 1.5, p < 0.05). The proportion of Tc, NK, NKT-like, and HLADR positive T cells were elevated in OSA patients when compared with healthy subjects (36.4 versus 26.8, 15.5 versus 8.5, 5.7 versus 3.0, and 8.4 versus 4.5%, p < 0.05, resp.) and were more pronounced in patients with metabolic syndrome. The grade of OSA complication score correlated with systemic inflammation markers and the proportion of B cells. The value of adiponectin/BMI ratio correlated significantly with SpO2 (r = 0.31, p < 0.05), CRP (r = -0.35, p < 0.05), TNFα concentration (r = -0.36, p < 0.05), and proportion of B cells (r = 0.32, p < 0.05)., Conclusion: Lymphocytes B, Tc, NK, NKT-like, and adiponectin are involved in systemic immune response in OSA patients possibly predisposing them to cardiovascular and metabolic complications.

Introduction: Efficacy of chronic cough treatment is ambiguous. The aim of the study was to analyze chronic cough alleviation after specific treatment and the relationship between cough etiology and treatment efficacy., Material and Methods: A stepwise diagnostic approach was used to diagnose cough etiology in non-smoking adults with chronic cough. In all patients specific treatment was applied. Two different questionnaires - a visual analog scale and a 5-degree scale - were used to assess cough severity before and after 4-6 months of treatment., Results: A significant correlation between pre-treatment and post-treatment results of both questionnaires was found (Spearman coefficient 0.43, p = 0.0003 and 0.73, p < 0.0001, respectively). Baseline questionnaire analysis revealed no differences in cough severity between patients with different cough causes or multiple cough causes. Although specific treatment resulted in a significant decrease of cough severity in the entire group, only partial improvement was noted. According to the visual analogue scale, a decrease of cough severity by at least 50% was achieved only in 54.4% of patients (37/68). Similarly, satisfactory improvement was noted in only 54.4% (37/68) of patients when using the 5-point scale. There were three sub-groups of patients, in whom no relevant decrease of cough severity was observed despite treatment: patients with 1. three coexisting cough causes, 2. non-asthmatic eosinophilic bronchitis, and 3. chronic idiopathic cough., Conclusions: Cough severity does not depend on its etiology. Efficacy of chronic cough treatment in non-smoking patients is only moderate.