Lung Cancer in Women-Sociodemographic, Clinical and Psychological Characteristics with Comparison to Men.

(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 Sklodowska-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.

Flow Cytometric Analysis of Macrophages and Cytokines Profile in the Bronchoalveolar Lavage Fluid in Patients with Lung Cancer.

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-1ß, IL-12, IL-23, and TGF-ß) 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.

Coping styles with stress and its relations to psychiatric and clinical symptoms in patients with sarcoidosis: A latent profile analysis.

OBJECTIVE: Although stress and styles of coping with it can have a major impact on one's health and can determine the course and management of chronic diseases, no previous studies have evaluated coping strategies and their relation to emotional distress and clinical symptoms in sarcoidosis. METHODS: In two consecutive studies, we investigated differences in coping styles of sarcoidosis patients in comparison to healthy control subjects and the association of identified profiles to an objective measurement of disease (Forced Vital Capacity) and symptoms such as dyspnoea, pain, anxiety and depressive symptoms in 36 patients with sarcoidosis (study 1) and 93 patients with sarcoidosis (study 2). RESULTS: Across two studies we found that patients with sarcoidosis used emotion-focused and avoidant coping significantly less often than healthy individuals, and that in both groups the profile with dominant problem (task)-focus style was the most beneficial in terms of mental health. Further, the profile of sarcoidosis patients characterized by the lowest intensity of all coping strategies was found to be superior in terms of physical health status (dyspnoe, pain and FVC level). CONCLUSION: These findings suggest that successful management of sarcoidosis should include coping styles assessment and call for a multidisciplinary approach in diagnosis and treatment of sarcoidosis patients.

Sex differences in clinico-pathologic characteristics and long-term survival among 17,192 surgically treated NSCLC patients: Nationwide population-based propensity score-matching study.

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.

Lung Cancer in the Course of COPD-Emerging Problems Today.

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.

Estrogens, Cancer and Immunity.

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.

Effector Memory T Cells and CD45RO+ Regulatory T Cells in Metastatic vs. Non-Metastatic Lymph Nodes in Lung Cancer Patients.

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.

Myeloablative Conditioning for Transplantation Induces State of Sterile Inflammation in the Bone Marrow: Implications for Optimizing Homing and Engraftment of Hematopoietic Stem Cells.

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.

Immunosuppressive properties of human PD-1 + , PDL-1 + and CD80 + dendritic cells from lymph nodes aspirates of lung cancer patients.

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.

The clinico-pathological characteristics of surgically treated young women with NSCLC.

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.

Characterization of Extracellular Vesicles from Bronchoalveolar Lavage Fluid and Plasma of Patients with Lung Lesions Using Fluorescence Nanoparticle Tracking Analysis.

The current lack of reliable methods for quantifying extracellular vesicles (EVs) isolated from complex biofluids significantly hinders translational applications in EV research. The recently developed fluorescence nanoparticle tracking analysis (FL-NTA) allows for the detection of EV-associated proteins, enabling EV content determination. In this study, we present the first comprehensive phenotyping of bronchopulmonary lavage fluid (BALF)-derived EVs from non-small cell lung cancer (NSCLC) patients using classical EV-characterization methods as well as the FL-NTA method. We found that EV immunolabeling for the specific EV marker combined with the use of the fluorescent mode NTA analysis can provide the concentration, size, distribution, and surface phenotype of EVs in a heterogeneous solution. However, by performing FL-NTA analysis of BALF-derived EVs in comparison to plasma-derived EVs, we reveal the limitations of this method, which is suitable only for relatively pure EV isolates. For more complex fluids such as plasma, this method appears to not be sensitive enough and the measurements can be compromised. Our parallel presentation of NTA-based phenotyping of plasma and BALF EVs emphasizes the great impact of sample composition and purity on FL-NTA analysis that has to be taken into account in the further development of FL-NTA toward the detection of EV-associated cancer biomarkers.

Modulation of the immune response by heterogeneous monocytes and dendritic cells in lung cancer.

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.

Lung Cancer Stem Cells-Origin, Diagnostic Techniques and Perspective for Therapies.

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.

Identification of PD-1 ligands: PD-L1 and PD-L2 on macrophages in lung cancer milieu by flow cytometry.

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.

Blood Monocyte Subsets with Activation Markers in Relation with Macrophages in Non-Small Cell Lung Cancer.

(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.

Lung cancer in women in 21th century.

Lung cancer is the first cause of death from malignant disease. The distressing epidemiological data show the increasing female to male incidence ratio for this tumor. A high incidence of lung cancer in never smokers with importance of environmental agents makes a problem among women. Adenocarcinoma (ADC) is noted in women with increasing rate and ethnic background impacts female lung cancer with differences in the incidence of genetic aberrations. The conception of different hormonal status is taken into consideration as potential explanation of variant cancer biology and clinical manifestation in women and men. The impact of 17-ß-estradiol, estrogen receptors, aromatase expression, pituitary sex hormones receptors in carcinogenesis with relation between estrogens and genetic aberrations are investigated. The response to newest therapies among female is also different than in men. This overview summarizes currently available evidence on the specificity of female lung cancer and presents the direction of necessary studies.

Immunotherapy of solid tumors: safety of treatment.

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 immune­related 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.

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates.

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.