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Journal of Inflammation (London,... Feb 2024Mucosal-associated invariant T (MAIT) cells are an atypical subset of T lymphocytes, which have a highly conserved semi-constant αβ chain of T-cell receptor (TCR) and... (Review)
Review
Mucosal-associated invariant T (MAIT) cells are an atypical subset of T lymphocytes, which have a highly conserved semi-constant αβ chain of T-cell receptor (TCR) and recognize microbe-derived vitamin B metabolites via major histocompatibility complex class I related-1 molecule (MR1). MAIT cells get activated mainly through unique TCR-dependent and TCR-independent pathways, and express multiple functional and phenotypic traits, including innate-like functionality, T helper (Th) 1 cell immunity, Th 17 cell immunity, and tissue homing. Given the functions, MAIT cells are extensively reported to play a key role in mucosal homeostasis and infectious diseases. In the current work, we review the basic characteristics of MAIT cells and their roles in mucosal homeostasis and development of respiratory infectious diseases as well as their potential therapeutic targets.
PubMed: 38419084
DOI: 10.1186/s12950-024-00376-z -
European Journal of Cancer (Oxford,... Jan 2024Checkpoint inhibitor (CI) therapy has revolutionized treatment for non-small cell lung cancer (NSCLC). However, a proportion of patients do not respond to CI therapy for...
INTRODUCTION
Checkpoint inhibitor (CI) therapy has revolutionized treatment for non-small cell lung cancer (NSCLC). However, a proportion of patients do not respond to CI therapy for unknown reasons. Although the current paradigm in anti-tumor immunity evolves around T cells, the presence of tertiary lymphoid structures and memory B cells has been positively correlated with response to CI therapy in NSCLC. In addition, double negative (DN) (CD27 IgD) B cells have been shown to be abundant in NSCLC compared to healthy lung tissue and inversely correlate with the intratumoral presence of memory B cells. Nonetheless, no study has correlated DN B cells to survival in NSCLC.
METHODS
In this study, we evaluated the presence and phenotype of B cells in peripheral blood with flow cytometry of patients with NSCLC and mesothelioma before receiving CI therapy and correlated these with clinical outcome.
RESULTS
Non-responding patients showed decreased frequencies of B cells, yet increased frequencies of antigen-experienced CD21- DN (Atypical) B cells compared to responding patients and HC, which was confirmed in patients with mesothelioma treated with CI therapy.
CONCLUSIONS
These data show that the frequency of CD21- DN B cells correlates with lack of response to CI therapy in thoracic malignancies. The mechanism by which CD21- DN B cells hamper CI therapy remains unknown. Our findings support the hypothesis that CD21- DN B cells resemble phenotypically identical exhausted B cells that are seen in chronic infection or function as antigen presenting cells that induce regulatory T cells.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B-Lymphocytes; Phenotype; Mesothelioma
PubMed: 38039777
DOI: 10.1016/j.ejca.2023.113428 -
Cancers Jan 2024Atypical chronic lymphocytic leukemia (CLL) is still defined according to morphological criteria. However, deviance from the typical surface immunological profile...
Atypical chronic lymphocytic leukemia (CLL) is still defined according to morphological criteria. However, deviance from the typical surface immunological profile suggests an atypical immunological-based CLL. A large cohort of patients with CLL was retrospectively evaluated aiming at assessing morphological (FAB criteria), immunophenotypical (two or more discordances from the typical profile), and clinical-biological features of atypical CLL. Compared to typical cases, morphologically atypical CLL showed a greater percentage of unmutated IgVH and CD38 positivity, and a higher expression of CD20. Immunophenotypically atypical CLL was characterized by more advanced clinical stages, higher expression of CD20, higher rate of FMC7, CD79b and CD49d positivity, and by an intermediate-high expression of membrane surface immunoglobulin, compared to typical cases. When patients were categorized based on immunophenotypic and morphologic concordance or discordance, no difference emerged. Finally, morphological features better discriminated patients' prognosis in terms of time-to-first treatment, while concordant atypical cases showed overall a worse prognosis. Discordant cases by immunophenotype and/or morphology did not identify specific prognostic groups. Whether-in the era of molecular markers used as prognostic indicators-it does make sense to focus on morphology and immunophenotype features in CLL is still matter of debate needing further research.
PubMed: 38275909
DOI: 10.3390/cancers16020469 -
Frontiers in Immunology 2024Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as , , , and were known to cause familial hemophagocytic lymphohistiocytosis (FHL)....
Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as , , , and were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of and genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.
Topics: Adult; Humans; Lymphohistiocytosis, Hemophagocytic; Pore Forming Cytotoxic Proteins; Lymphoma, T-Cell, Peripheral; Killer Cells, Natural; Germ Cells; Membrane Proteins
PubMed: 38404589
DOI: 10.3389/fimmu.2024.1365975 -
Frontiers in Medicine 2023Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are rare in Asian countries. The histopathological diagnosis of LM is often challenging, and misdiagnosis is...
INTRODUCTION
Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are rare in Asian countries. The histopathological diagnosis of LM is often challenging, and misdiagnosis is common. Although histopathologic features of LM/LMM are known, statistical analysis of them were scarcely reported. In this study, we aimed to investigate the histopathological characteristics of LM/LMM in Korean patients and identify key histopathological clues distinguishing LM from benign lentigo.
METHODS
We performed a retrospective study of the clinical and histopathological features of patients diagnosed with LM/LMM at our center between 2011 and 2022. We assessed the histopathological features in each case based on 16 pathological criteria according to previous literature. Pathologically confirmed cases of benign lentigo were analyzed for comparison.
RESULTS
Twenty-one patients (10 with LM and 11 with LMM) were analyzed. Several statistically significant difference existed between the features of LM and benign lentigo ( = 10), including asymmetry of overall structure ( < 0.001), cytologic atypia ( < 0.001), predominant single-cell proliferation ( < 0.001), melanocytic nests ( = 0.033), melanocytes forming rows ( = 0.003), pagetoid spread of melanocytes ( < 0.001), and hair follicle invasion by atypical melanocytes ( < 0.001). Degree of solar elastosis was more severe in group "Age ≥ 60" ( = 0.015), and group "Diameter ≥ 20 mm" ( = 0.043). Presence of elongated rete ridges were less common in the older than 60 age group ( = 0.015) and group "Diameter ≥ 20 mm." Invasion was associated with mitosis ( = 0.001, OR 49.285), multinucleated cells ( = 0.035, OR 17.769), and degree of lymphocyte infiltration ( = 0.004).
CONCLUSION
This study investigated the clinical and histopathologic characteristics of LM and LMM in Koreans. Although histopathological diagnosis is challenging, especially in the early stages of LM, our data showed essential histopathological changes in architectural, cytological, and dermal patterns. Considering the potential aggressiveness of LM/LMM, it is essential to recognize its histopathological features and provide timely management.
PubMed: 38249976
DOI: 10.3389/fmed.2023.1249796 -
Frontiers in Immunology 2024Chagas disease is a neglected parasitic disease caused by . While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).
INTRODUCTION
Chagas disease is a neglected parasitic disease caused by . While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).
METHODS
Here, we employed high-dimensional flow cytometry to analyze CD4 T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.
RESULTS
Effector CD27CD4 T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4 T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4 T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.
DISCUSSION
Taken together, our results showed that infection triggers changes in CD4 T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.
CONCLUSION
Overall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.
Topics: Humans; Chagas Cardiomyopathy; Male; Middle Aged; Female; CD4-Positive T-Lymphocytes; Adult; B-Lymphocytes; Trypanosoma cruzi; Chronic Disease; Aged; Lymphocyte Activation
PubMed: 38726014
DOI: 10.3389/fimmu.2024.1385850 -
Clinical, Cosmetic and Investigational... 2023We present the case of a 37-year-old male diagnosed with Mycosis fungoides (MF) after gradually developing multiple skin tags and brownish lichenoid papules. The patient...
We present the case of a 37-year-old male diagnosed with Mycosis fungoides (MF) after gradually developing multiple skin tags and brownish lichenoid papules. The patient had pre-existing erythema over his entire body, especially his face, upper extremities, and trunk, for over 1.5 years. Microscopic examination of the papule and the skin tag (ST) exhibited similar features mainly characterized by superficial dense band-like lymphoid infiltrates and epidermotropism of atypical lymphocytes (Pautrier's micro-abscesses). Immunohistochemistry further revealed the lymphoid infiltrates predominantly expressed LCA, CD3, CD4, and CD45RO but lacked CD7, CD8, CD30, CD20, and CD79a. The finding of this study that reports MF characterized by unusual STs suggests that some causes and effects have not been previously described in MF.
PubMed: 37441694
DOI: 10.2147/CCID.S411041 -
In Vivo (Athens, Greece) 2024Among the four genomic subtypes of endometrial cancer, distinguishing between the DNA polymerase epsilon mutation (POLEmut) and no specific molecular profile (NSMP)...
BACKGROUND/AIM
Among the four genomic subtypes of endometrial cancer, distinguishing between the DNA polymerase epsilon mutation (POLEmut) and no specific molecular profile (NSMP) subtypes requires genomic profiling owing to the lack of surrogate immunohistochemical markers. We have previously found that, histologically, the POLEmut-subtype exhibits surface epithelial slackening (SES). Therefore, to improve subtype identification, we aimed to extract cytological features corresponding to SES in POLEmut-subtype cervical cytology specimens.
MATERIALS AND METHODS
We analyzed 104 endometrial cancer cervical cytology specimens, with integrative diagnosis confirmation via histology, immunohistochemistry, and genomic profiling. Cytological features were evaluated for the presence of atypical glandular cells, atypical cell appearance in single cells and clusters, and cytological SES and the presence of tumor-infiltrating inflammatory cells in clusters.
RESULTS
Based on cervical cytology, the POLEmut- and p53mut-subtypes exhibited more frequent atypical cells in smaller clusters, giant tumor cells, and cytological SES patterns than the NSMP-subtype. Tumor-infiltrating lymphocytes were frequent in the POLEmut- and mismatch repair-deficient subtypes.
CONCLUSION
Histologically-detected SES as well as other endometrial cancer features may be preserved in the atypical cell clusters observed in cervical cytology specimens. Cytological detection of SES and of smaller clusters of atypical cells and inflammatory cells with moderate atypia are suggestive of POLEmut-subtype. Integrative diagnosis including genomic profiling remains critical for diagnostic confirmation.
Topics: Female; Humans; Cervix Uteri; Endometrial Neoplasms; Endometrium; Immunohistochemistry; Mutation; DNA Polymerase II; Poly-ADP-Ribose Binding Proteins
PubMed: 38148087
DOI: 10.21873/invivo.13442 -
The Journal of Allergy and Clinical... Jan 2024Repetitive or persistent cellular stimulation in vivo has been associated with the development of a heterogeneous B-cell population that exhibits a distinctive... (Review)
Review
Repetitive or persistent cellular stimulation in vivo has been associated with the development of a heterogeneous B-cell population that exhibits a distinctive phenotype and, in addition to classical B-cell markers, often expresses the transcription factor T-bet and myeloid marker CD11c. Research suggests that this atypical population consists of B cells with distinct B-cell receptor specificities capable of binding the antigens responsible for their development. The expansion of this population occurs in the presence of chronic inflammatory conditions and autoimmune diseases where different nomenclatures have been used to describe them. However, as a result of the diverse contexts in which they have been investigated, these cells have remained largely enigmatic, with much ambiguity remaining regarding their phenotype and function in humoral immune response as well as their role in autoimmunity. Atypical B cells have garnered considerable interest because of their ability to produce specific antibodies and/or autoantibodies and because of their association with key disease manifestations. Although they have been widely described in the context of adults, little information is present for children. Therefore, the aim of this narrative review is to describe the characteristics of this population, suggest their function in pediatric immune-related diseases and chronic infections, and explore their potential therapeutic avenues.
Topics: Adult; Humans; Child; B-Lymphocytes; Communicable Diseases; Autoimmune Diseases; Autoantibodies; Receptors, Antigen, B-Cell; Autoimmunity
PubMed: 37890706
DOI: 10.1016/j.jaci.2023.10.009 -
Microorganisms Feb 2024microRNAs (miRNAs) are small non-coding RNAs (sncRNAs) that play an important role in the life cycle of human viruses. We sought to characterize human immunodeficiency...
microRNAs (miRNAs) are small non-coding RNAs (sncRNAs) that play an important role in the life cycle of human viruses. We sought to characterize human immunodeficiency virus 1 (HIV-1)-encoded miRNAs and determine their role in viral replication. Initially, a bioinformatic analysis was used to predict HIV-1-encoded miRNAs. Next, a representative number of these predicted sequences were verified using a miRNA microarray chip, reverse transcription PCR (RT-PCR), and the deep sequencing of RNA extracted from HIV-1-infected cells. Eight HIV-1-encoded sncRNA sequences conforming to the criteria that define miRNAs were identified in HIV-1-infected immortalized T cells and human primary CD4+ lymphocytes; five of the eight sequences have not been previously reported. Deep sequencing validated the presence of these virus-encoded miRNA sequences and uncovered large numbers of atypical sncRNA sequences, lacking characteristics of conventional miRNAs. We named these sequences small RNAs (smRNAs). The overexpression of four candidate HIV-1-encoded miRNAs and silencing of two smRNAs significantly increased HIV-1 viral replication. Our study uncovered novel HIV-1-encoded sncRNAs that, upon deregulated expression, alter viral titers in HIV-1-infected cells, suggesting that miRNAs and smRNAs play an important role in regulating viral replication. Future studies may reveal the function of HIV-1-encoded sncRNAs and their possible implications for diagnosis and treatment.
PubMed: 38543476
DOI: 10.3390/microorganisms12030425