Participation of B cell in immunotherapy of cancer

Pathology - Research and Practice, Год журнала: 2024, Номер 255, С. 155169 - 155169

Опубликована: Янв. 26, 2024

Язык: Английский

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Allergen immunotherapy in asthma

Allergology International, Год журнала: 2024, Номер 73(4), С. 487 - 493

Опубликована: Июль 1, 2024

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma indicated in cases HDM-sensitized normal lung function. improves symptoms AHR, decreases medication dose. Importantly, AIT can improve other complicated by asthma, such as rhinitis, also contribute improvement symptoms. Several studies suggested HDM-SLIT attenuates risk exacerbations, function rhinitis. Furthermore, modify natural course diseases, asthma. For example, effects are maintained at least several years after discontinuation. prevent onset when introduced inhibit or reduce new allergen sensitizations. Recent data may suppress non-targeted allergen-induced immune responses addition targeted responses, infections lower respiratory tract enhancing IFN responses.

Язык: Английский

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Novel Frontiers in Regulatory B cells

Immunological Reviews, Год журнала: 2021, Номер 299(1), С. 5 - 9

Опубликована: Янв. 1, 2021

The number of regulatory B cell "followers" has increased steadily in the last few years confirming rising interest understanding relevance this subset cells controlling immune responses a variety immune-related diseases. Regulatory (Breg) are potent modulators responses, which prevent excessive inflammation and maintain homeostasis after infection or tissue-injury.1 Abnormalities Breg function have been identified pathologies such as autoimmune disease, chronic infections, cancer, rejection transplants.1, 2 Thus, it is utmost clinical importance to understand ontogeny these populations, phenotypically characterize cellular signals molecular "cues," drive differentiation. By better characterizing populations processes leading their differentiation, we can identify target molecules/pathways for therapeutic interventions pathologies. first manuscript describing existence with suppressive dates back 1970's, where was described studies examining delayed-type hypersensitivity (DTH) reactions using either 2,4 dinitrofluorobenzene (DNFB) ovalbumin (OVA) incomplete Freund's adjuvant (IFA) paraeminobenzoic acid-Hen egg albumin conjugate (PABA-HEA) guinea pigs. Increased intensity prolonged DTH were observed cell-depleted DNFB-sensitized pigs.3 Later showed that adoptive transfer lymphocytes total splenocytes suppressed response.4, 5 These dubbed "suppressor cells." However, mechanisms behind response never investigated study regulation not renewed until 1990's, when late Charles Janeway his team cell-deficient mice developed an exacerbated form experimental encephalomyelitis (EAE).6 It 10 later almost simultaneously three papers revisited concept suppressors different diseases term coined.7-9 Nevertheless, field remained stalled several cell-depletion therapies trialed proved efficacious rheumatic therapy (BCT) originates from cancer used clinic remove hematological malignancies.10 A pioneering conducted at University College, London, early 2000's, confirmed efficacy rituximab had ameliorating disease small patients refractory rheumatoid arthritis (RA).11 This initial followed by trials showing treatment arthritis, systemic lupus erythematosus, more recently multiple sclerosis (MS).12-14 majority focusing on how depletion work showed, somewhat surprisingly, autoantibodies known play important part pathogenesis remain largely unaltered depletion. results reignited contribute through antibody-independent including antigen processing cytokine/chemokine production. Twenty later, thought timely dedicate entire volume underappreciated subset, regulates many body. In volume, experts discuss reconcile issues related identification Bregs, whether Bregs lineage-specific if they arise any stage maturation microenvironmental "cues"; tissue location tissue-associated pathology differentiation; need interaction other shape differentiation (Figure 1). (Bregs) role control inflammation, IL-10 production considered be hallmark identification. universal surface marker, captures functional heterogeneity human murine subsets, so far evaded discovery.1, 15 particular, all know flow cytometry, example, confronted highly heterogeneous population regardless its developmental stage, appropriate signal, become suppressive. Ma et al16 provide phenotypical overview subsets reported. authors describe phenotypes allergic conditions food allergy atopic dermatitis. They show whereas CD9-expressing preventive both mouse models asthma,17, 18 CD5-expressing TGFβ-producing implicated dermatitis.19 also touch upon change according stimuli residency, thus justifying gaining insight field, order develop targeted disease. An example utility harnessing allergies allergen-specific immunotherapy. Beekeepers tolerized bee venom allergen phospholipase A2, frequencies IL-10+IgG4+CD25hiCD71hiCD73- (BR1) compared healthy controls. Remarkably, numbers BR1 receiving specific immunotherapy, linking maintenance tolerance against allergens.20 Cherukuri al21 proposed TIM-1 shared marker transplantation. explore detail unique promoting upregulation inhibitory cytokines receptors previously ascribed function, well implemented improve allograft survival. group points persistent challenge remaining only around 5% peripheral blood express TIM-1.16 Despite continuous lack unifying markers, mechanistic translational progress made. Rothstein colleagues reported encouraging findings IL-10/TNF (Breg:B effector) ratio biomarker prediction outcomes undergoing transplantation; decreased IL-10+Bregs.21 interesting into effects immunosuppressive agents current conundrum faced immune-suppressive field; promote while depleting pathogenic cells? Further elucidation required would help us address question. Multiple (MS) historically T cell-driven disease; however, recent undeniable success amelioration MS clearly shows involvement disease.22, 23 Wang al24 balanced resume complex interplay protective evidence producing neuroinflammation EAE model.8 Since study, roles functions plasmablasts (PB) plasma (PC) documented EAE.25, 26 al nicely tie old latest discovery gut microbiota, IgA+ cells. "theoretical platform" discussing potential PCs, post-rituximab therapy, amelioration. contributions neuroinflammation, factors impact development, maintenance, migration will rationalizing next-generation cell-directed MS. played tissues/organs still under-investigation. key sentinels mucosal sites local release antibodies presentation antigen. Menon al27 detailed state-of-knowledge mucosa-associated lymphoid (MALT) lung state sparsely present but result predominantly found ectopic tissues (ELT).28 Importantly, proinflammatory anti-inflammatory roles, dependent cues receive abnormalities and/or well-documented various Topically, highlight research severe Sars-Cov2 infection, IL-10+Bregs suggested immunopathology.27, 29 Immune evasion tumor major problem design therapeutics successful solid cancers.30 well-established immunotolerant environment, contributes evasion.30 autoimmunity, numerically deficient functionally impaired,2 contribution tumors infancy. Mounting increasingly intra-tumor cancer.31 report tumor-infiltrating IL-10+Breg, suppressing tumoricidal lungs patients.32, 33 Michaud al31 pro anti-tumorigenic respectively anti-tumor microenvironment. minutely review existing literature recruited take advantage armory increase cytotoxity killing tumor-target. clearance via antibody-dependent cytotoxicity (ADCC) facilitating phagocytosis dendritic cells; enhancing antigens cytokines.34-36 On hand, IL-35 enhancement already immune-tolerogenic environment tumors. propose could exploited treatment, how, selectively targeting IL-35-expressing require direct exert function. interact CD4+ inhibit Th1 Th17 cells, development FoxP3+Tregs. suppress IL-12 TNFα monocytes, cytotoxic CD8+ cells.1 most discovered type cross-talk invariant natural killer (iNKT)37, 38; bridging innate adaptive pathogens providing homeostasis.39 Leadbetter Karlsson thorough covering aspects iNKT outcome encounter leads generation (iNKTreg)15 follicular helper (iNKTFH) turn support pathogen-specific effector differentiation.40 addition, extensive iNKT-B interactions modulating presented. cognate helps tumor-specific antibodies.41 Conversely, downregulation CD1d leukemia lytic cells.42-44 Whether induce context remains determined. Targeted increasing expression activity Examining nature presented cell:iNKT therapy. formation antigen-specific clones incremental receptor affinity given process humoral immunity viral pathogens. review, Burton Maini, hepatitis core (HBcAg) (HBsAg), outline load properties lead memory what determines clone proceeds germinal center (GC) reaction extrafollicular pathway.45 Chronic characterized exhaustion virus-specific delve dysregulation GC preference enter pathway, evidenced long-lived formation. Key fate decision prefollicular elucidate mechanism skewing CD4 away archetypical phenotype, thereby responses. Lastly, forming intrahepatic atypical patients. Taken together, articles beyond autoantigens infections cancer. issue provides insights action novel between system currently inform drug development. ontogeny, pathways researchers overcome caveats broad-spectrum approaches specifically leaving intact.

Язык: Английский

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Mechanisms in AIT: Insights 2021

Allergologie select, Год журнала: 2022, Номер 6(01), С. 259 - 266

Опубликована: Янв. 1, 2022

Allergen-specific immunotherapy (AIT) is currently the only treatment with potential long-term disease-modifying effects for patients suffering from allergic diseases such as rhinitis, asthma, venom allergy, or IgE-mediated food allergy. A better understanding of molecular mechanisms underlying immune responses during successful AIT utmost importance and it may help to develop more effective safer treatments.PubMed literature review was performed using keywords allergen-specific immunotherapy; regulatory T cells; B innate lymphoid antibody years 2018 2021.The proposed mechanism tolerance induction in AIT, even upon discontinuation, involves basophils, mast cells, dendritic downregulation effector type 2 responses, decrease production IgE increase blocking antibodies, IgG2 IgG4.We summarize most recent advances related involved restoration healthy allergens AIT. Our knowledge this regard has significantly improved over last years, which might well contribute design novel therapeutic approaches.

Язык: Английский

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A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders

Allergy, Год журнала: 2022, Номер 77(11), С. 3267 - 3292

Опубликована: Июль 17, 2022

The inflammation of allergic diseases is characterized by a complex interaction between type 2 and 3 immune responses, explaining clinical symptoms histopathological patterns. Airborne stimuli activate the mucosal epithelium to release number molecules impacting activity resident environmental cells. Signals from barrier, regulatory cells, inflamed tissue are crucial conditions able modify innate adaptive effector cells providing selective homing eosinophils or neutrophils. high plasticity T- lymphoid responding external signals prerequisite explain multiplicity endotypes diseases. This notion paved way for huge use specific biologic drugs interfering with pathogenic mechanisms inflammation. Based on response epithelial functions structural non-lymphoid this review proposes some immunopathogenic scenarios characterizing principal which can be associated precise phenotype asthma. Recent literature indicates that similar concepts also applied other non-respiratory disorders. next challenges will consist in defining biomarker(s) each endotype allowing quick diagnosis most effective personalized therapy.

Язык: Английский

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