RESUMO
Tuberculosis, caused by Mycobacterium tuberculosis, remains an enduring global health challenge due to the limited efficacy of existing treatments. Although much research has focused on immune failure, the role of host macrophage biology in controlling the disease remains underappreciated. Here we show, through multi-modal single-cell RNA sequencing in a murine model, that different alveolar macrophage subsets play distinct roles in either advancing or controlling the disease. Initially, alveolar macrophages that are negative for the CD38 marker are the main infected population. As the infection progresses, CD38+ monocyte-derived and tissue-resident alveolar macrophages emerge as significant controllers of bacterial growth. These macrophages display a unique chromatin organization pre-infection, indicative of epigenetic priming for pro-inflammatory responses. Moreover, intranasal BCG immunization increases the numbers of CD38+ macrophages, enhancing their capability to restrict Mycobacterium tuberculosis growth. Our findings highlight the dynamic roles of alveolar macrophages in tuberculosis and open pathways for improved vaccines and therapies.
Assuntos
ADP-Ribosil Ciclase 1 , Pulmão , Macrófagos Alveolares , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis , Animais , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/metabolismo , Mycobacterium tuberculosis/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/genética , Modelos Animais de Doenças , Feminino , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/imunologia , Vacina BCG/imunologia , Análise de Célula Única , Tuberculose/imunologia , Tuberculose/microbiologiaRESUMO
BACKGROUND: Intravesical bacillus Calmette-Guerin (IVBCG) is considered the most optimal follow-up therapy for high-risk urothelial cancers. Although side effects such as cystitis, hematuria, and low-grade fever are common, they are generally mild. Severe reactions involving the kidneys are extremely rare. Here, we present the case of a 64-year-old male who developed acute renal failure due to acute tubulointerstitial nephritis (ATIN) following the first IVBCG administration. We have also conducted a literature review concerning IVBCG-induced nephritis. CASE REPORT: A 64-year-old male presented to the Nephrology Department with acute kidney injury indicators and hematuria. The patient was suffering from high-grade papillary urothelial carcinoma. Transurethral resection of the bladder tumor was performed twice and followed by one IVBCG administration - two days before the symptoms occurred. The latest follow-up cystoscopy excluded the recurrence of the cancer. Laboratory tests displayed hyperkalemia, decreased glomerular filtration rate (GFR = 4 ml/min/1.73 m2), elevated C-reactive protein, and acute metabolic acidosis. Urinalysis showed proteinuria (900 mg/24 h), leukocyturia, and erythrocyturia (20,402.7 per microliter). Renal ultrasound demonstrated slight bilateral renal enlargement. The patient was identified with acute tubulointerstitial nephritis (ATIN). The treatment involved intravenous methylprednisolone (250 mg three times every two days and then 125 mg four times every two days), fol-lowed by oral methylprednisolone (24 mg and 12 mg daily alternately for a week). Piperacillin and tazobactam, probiotics, and proton pump inhibitors were also administered. Hemodialysis was conducted three times. Two weeks after the admission, a significant improvement was observed: creatinine decreased to 2.04 mg/dl, and GFR increased to 33 ml/min/1.73 m2. The patient was discharged with a recommendation to reduce the dose of glucocorticosteroids and continued in the outpatient clinic. CONCLUSIONS: IVBCG may lead to acute kidney injury due to ATIN. Symptoms may occur as early as after the first IVBCG, contrary to previous reports. Patients should be regularly assessed for potential complications, including creatine level measurement, after each IVBCG treatment.
Assuntos
Injúria Renal Aguda , Vacina BCG , Nefrite Intersticial , Humanos , Masculino , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Pessoa de Meia-Idade , Vacina BCG/efeitos adversos , Vacina BCG/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração IntravesicalRESUMO
BACKGROUND: The BCG vaccine has been traditionally administered to prevent TB. It has been additionally used in bladder cancer patients as a therapy with success. Some observational studies found that bladder cancer patients receiving BCG may have reduced dementia risk, however, the evidence is not conclusive. OBJECTIVE: To investigate the impact of BCG vaccine on dementia risk in bladder cancer patients. METHODS: Six databases were searched from inception to January 13, 2024, for published and unpublished studies that examine the association between BCG and dementia risk in bladder cancer patients. We conducted meta-analyses using a random-effects model. RESULTS: Eight retrospective cohort studies were included in the systematic review and seven in the meta-analyses. Because there were studies with overlapping populations, two separate main analyses were performed reassuring the avoidance of overlap. The first analysis showed that compared to controls, BCG did not reduce dementia risk [5 studies pooled, n=88,852, HR = 0.65, 95% CI (0.40, 1.06), I2 = 85%] whereas there was a marginally significant risk reduction in the second analysis [6 studies pooled, n=70,025, HR = 0.63, 95% CI (0.40, 0.97), I2 = 83%]. Sensitivity analysis excluding the unpublished studies did not affect the outcome importantly. Additional meta-analysis showed that BCG did not reduce the risk of Alzheimer's disease. CONCLUSION: This meta-analysis of observational studies found that BCG administration in bladder cancer patients has likely a minimally positive impact on dementia risk if any. To better understand the effect of BCG on dementia, randomized controlled trials are needed.
Assuntos
Vacina BCG , Demência , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/prevenção & controle , Humanos , Vacina BCG/administração & dosagem , Demência/prevenção & controleRESUMO
Aging leads to alterations that precipitate or aggravate several diseases that occur across our lifespan. In the CNS, aging affects the capacity to maintain and repair the myelin sheaths that protect axons and facilitate neuronal signaling. Tiwari et al. report aging-associated transcriptional responses in microglia after demyelination, which could be reversed by epigenetic remodeling after BCG vaccination.
Assuntos
Envelhecimento , Vacina BCG , Bainha de Mielina , Remielinização , Vacina BCG/imunologia , Humanos , Envelhecimento/imunologia , Animais , Bainha de Mielina/imunologia , Bainha de Mielina/metabolismo , Microglia/imunologia , Doenças Desmielinizantes/imunologia , Epigênese Genética , Camundongos , VacinaçãoRESUMO
Tuberculosis (TB) is one of the leading causes of death from infectious diseases, killing approximately 1.3 million people worldwide in 2022 alone. The current vaccine for TB contains a live attenuated bacterium, Mycobacterium bovis BCG (Bacille Calmette-Guérin). The BCG vaccine is highly effective in preventing severe forms of childhood TB but does not protect against latent infection or disease in older age groups. A new or improved BCG vaccine for prevention of pulmonary TB is urgently needed. In this study, we infected murine bone marrow derived dendritic cells from C57BL/6 mice with M. bovis BCG followed by elution and identification of BCG-derived MHC class I and class II-bound peptides using tandem mass spectrometry. We identified 1436 MHC-bound peptides of which 94 were derived from BCG. Fifty-five peptides were derived from MHC class I molecules and 39 from class II molecules. We tested the 94 peptides for their immunogenicity using IFN- γ ELISPOT assay with splenocytes purified from BCG immunized mice and 10 showed positive responses. Seven peptides were derived from MHC II and three from MHC class I. In particular, MHC class II binding peptides derived from the mycobacterial surface lipoprotein Mpt83 were highly antigenic. Further evaluations of these immunogenic BCG peptides may identify proteins useful as new TB vaccine candidates.
Assuntos
Antígenos de Bactérias , Vacina BCG , Proteínas de Bactérias , Células Dendríticas , Camundongos Endogâmicos C57BL , Mycobacterium bovis , Animais , Antígenos de Bactérias/imunologia , Mycobacterium bovis/imunologia , Camundongos , Vacina BCG/imunologia , Proteínas de Bactérias/imunologia , Células Dendríticas/imunologia , Desenvolvimento de Vacinas , Feminino , Proteômica/métodos , Linfócitos T/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Lipoproteínas/imunologia , Tuberculose/prevenção & controle , Tuberculose/imunologia , Peptídeos/imunologia , Proteínas de MembranaRESUMO
OBJECTIVES: Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary. Furthermore, this data possesses important significance for practical applications associated with the development of recombinant BCG strains aimed to enhance innate immunity against diverse infectious agents. DATA DESCRIPTION: We performed RNA sequencing of innate immune cells derived from murine bone marrow and spleen three days after subcutaneous BCG vaccination. Using fluorescence-activated cell sorting we obtained three cell populations for each mouse from both control and BCG vaccinated groups: bone marrow monocytes and neutrophils and splenic NK-cells. Then double-indexed cDNA libraries for Illumina sequencing from the collected samples were prepared, the resulting cDNA library mix was subjected to NovaSeq 6000 sequencing. This paper describes the collection of 24 RNA sequencing samples comprising 4 sets of immune cell populations obtained from subcutaneously BCG-vaccinated and control mice.
Assuntos
Vacina BCG , Imunidade Inata , Baço , Transcriptoma , Animais , Vacina BCG/imunologia , Vacina BCG/administração & dosagem , Camundongos , Transcriptoma/genética , Baço/imunologia , Vacinação/métodos , Células Matadoras Naturais/imunologia , Camundongos Endogâmicos C57BL , Injeções Subcutâneas , Monócitos/imunologia , Feminino , Neutrófilos/imunologia , Análise de Sequência de RNA/métodos , Células da Medula Óssea/imunologiaRESUMO
BACKGROUND: Bladder cancer continues to be a significant health issue, leading to ongoing research into novel biomarkers and treatment strategies. This study aims to evaluate the potential of serum fibronectin levels and fibronectin gene polymorphisms as biomarkers for predicting the recurrence and treatment response in patients with NMIBC undergoing intravesical BCG therapy. METHODS: Between June 2022 and December 2022, data of 73 patients who applied to the Mersin University Urology Clinic due to NMIBC and were followed and treated in our clinic, receiving intravesical BCG treatment, when necessary, as well as 56 individuals without any malignancy, were prospectively examined. Serum fibronectin levels were measured using the enzyme-linked immunosorbent assay method. PCR testing was applied for the fibronectin gene RS10202709 and RS 35,343,655 gene polymorphisms by using Real-Time PCR. RESULTS: The mean serum fibronectin level in the patient group was 76.794 ± 66.998ng/ml. Simultaneously, it was 50.486 ± 25.156ng/ml in the control group, and these differences in serum fibronectin levels were statistically significant(p = 0.003). Out of the 73 patients included in the study, recurrence of bladder cancer was observed in 53 of them. They were divided into two groups based on the recurrence times: early recurrence and late recurrence. The mean fibronectin level in the early recurrence group was 102 ± 86.1 ng/ml, while it was 44.7 ± 11.8 ng/ml in the late recurrence group. Emphasize the significance of the higher fibronectin levels in the early recurrence group by stating, patients with early recurrence exhibited significantly higher serum fibronectin levels compared to those with late recurrence (p < 0.001), suggesting a potential role for fibronectin as a prognostic biomarker. CONCLUSIONS: The statistically higher concentrations of serum fibronectin levels in patients with bladder cancer observed in our study are a noteworthy finding. These findings suggest that serum fibronectin levels could serve as a valuable prognostic biomarker for early recurrence in NMIBC patients, although their predictive value for BCG treatment response remains limited.
Assuntos
Adjuvantes Imunológicos , Vacina BCG , Fibronectinas , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Fibronectinas/sangue , Vacina BCG/uso terapêutico , Vacina BCG/administração & dosagem , Masculino , Feminino , Administração Intravesical , Pessoa de Meia-Idade , Idoso , Prognóstico , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Polimorfismo Genético , Estudos Prospectivos , Recidiva Local de Neoplasia/sangue , Biomarcadores Tumorais/sangue , Neoplasias não Músculo Invasivas da BexigaRESUMO
BCG vaccination is known to be safe in infants and a part of immunization schedule in high tuberculosis (TB) burden countries. In the conquest to bring down the severity of the COVID 19 pandemic, many drugs were repurposed in research mode including BCG vaccination/revaccination in various populations. We did a study among the elderly population (>60 years of age) to assess the role of BCG revaccination in preventing the severity of COVID 19 disease. Live attenuated BCG vaccine was given to the willing participants and were followed up for 6 months to estimate COVID19 incidence, understand severity and immunogenicity profile. A total of 48 serious adverse events (SAE) were reported among 1566 elders, none of them had more than one SAE. None of the SAEs were related to the BCG revaccination. Among the 372 adverse events reported, 96% were local reactions at the vaccine site and resolved on its own. BCG revaccination appeared to be safe and could be explored further if repurposing studies were planned for other diseases.
Assuntos
Vacina BCG , COVID-19 , Imunização Secundária , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacina BCG/efeitos adversos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Incidência , Índia/epidemiologiaRESUMO
Tuberculosis (TB) is one of the main contributors to global mortality and morbidity. Prevalence of TB is more in developing countries. It is one of the airborne diseases that has always been a major health problem. It is caused by organisms of the Mycobacterium tuberculosis (MTB) complex affecting different organ systems. The proverb prevention is better than cure best applies to TB and it has been practiced from ancient periods. However, modalities of prevention have varied much depending upon the advancement in research and technology. TB preventive practice reduces the load of TB significantly and it was used as the theme for world TB Day for the year 2013. Bacille Calmette-Guérin (BCG) vaccination is one of the modalities to prevent TB and it's been practiced for decades with a lot of modifications from synthesis, schedule and method of administration. BCG mainly prevents serious TB with a less known effect on TB prevention. Other uses of BCG vaccination are being studied. In the modern era, heterologous effects of BCG vaccination have brought BCG once again into the limelight. TB prevention strategies start from basic health education and vaccination. Newer vaccines are under trial to improve the efficacy of TB vaccination and yet to be used for general practice. Prevention and immunization against TB have been modified in immunocompromised children. The concept of drug resistance has to be kept in mind before using anti tubercular drugs without any bacteriological evidence for tuberculosis. National Tuberculosis Elimination Programme (NTEP) focuses on contact tracing and treatment of latent TB infection as a resort to prevent further spread of TB in India. This review article has been authored following an exhaustive examination of the existing literature, with the aim of enhancing comprehension regarding tuberculosis prevention and immunization.
Assuntos
Vacina BCG , Tuberculose , Humanos , Vacina BCG/uso terapêutico , Criança , Tuberculose/prevenção & controle , Tuberculose/epidemiologia , Índia/epidemiologia , VacinaçãoRESUMO
The BCG vaccine, Bacille Calmette Guerin, holds the distinction of being the most widely administered vaccine. Remarkably, a century has passed since its discovery; however, puzzlingly, questions persist regarding the effectiveness of the immune response it triggers. After years of diligent observation, it has been deduced that BCG imparts immunity primarily to a specific age group, namely children. This prompts a significant query: the rationale behind BCG's limited efficacy against TB in particular age groups and populations remains elusive. Beyond vaccinations, drug therapy has emerged as an alternative route for TB prevention. Nonetheless, this approach faces challenges in the contemporary landscape, marked by the emergence of new instances of MDR-TB and XDR-TB, compounded by the financial burden of treatment. It's noteworthy that BCG remains the sole WHO-approved vaccine for TB. This comprehensive review delves into several aspects, encompassing the immune response during infection, the shortcomings of BCG in conferring immunity, and the various factors contributing to its limitations. Within this discourse, we explore potential explanations for the observed deficiencies of the BCG vaccine and consider how these insights could catalyze the development of future vaccines. The current landscape of novel vaccine development for TB is illuminated, including a spotlight on the latest vaccine candidates.
Assuntos
Vacina BCG , Vacinas contra a Tuberculose , Humanos , Vacina BCG/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/prevenção & controle , Desenvolvimento de Vacinas , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controleRESUMO
Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.
Assuntos
Vacina BCG , Hospedeiro Imunocomprometido , Vacinas Sintéticas , Animais , Vacina BCG/imunologia , Vacina BCG/efeitos adversos , Vacina BCG/genética , Camundongos , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Feminino , Tuberculose/prevenção & controle , Tuberculose/imunologia , Mycobacterium bovis/imunologia , Mycobacterium bovis/genética , Mycobacterium bovis/patogenicidade , Modelos Animais de Doenças , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Camundongos Endogâmicos C57BL , Pulmão/microbiologia , Pulmão/patologia , Pulmão/imunologia , Tuberculose Pulmonar/prevenção & controle , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Eficácia de VacinasRESUMO
Bacille Calmette-Guérin (BCG) vaccine has been used increasingly in immunotherapy, including treatment of non-muscle-invasive bladder cancer, as an adjuvant therapy in metastatic prostate cancer and metastatic melanoma. However, systemic infection from inadvertent intravenous (instead of intravesical) injection is uncommon and can have systemic ramifications. We encountered 3 patients with disseminated Mycobacterium bovis infection that ensued after intravenous BCG injection.
Assuntos
Vacina BCG , Mycobacterium bovis , Humanos , Vacina BCG/efeitos adversos , Vacina BCG/administração & dosagem , Masculino , Mycobacterium bovis/isolamento & purificação , Mycobacterium bovis/imunologia , Pessoa de Meia-Idade , Injeções Intravenosas , Tuberculose/tratamento farmacológico , Idoso , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children.
Assuntos
Vacina BCG , Mycobacterium bovis , Osteomielite , Humanos , Osteomielite/etiologia , Osteomielite/tratamento farmacológico , Osteomielite/diagnóstico , Osteomielite/microbiologia , Vacina BCG/efeitos adversos , Masculino , Mycobacterium bovis/isolamento & purificação , Antituberculosos/uso terapêutico , Lactente , Diagnóstico Diferencial , Vacinação/efeitos adversosRESUMO
Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs). Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles. Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV. Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals.
Assuntos
Programas de Imunização , Humanos , Lactente , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Esquemas de Imunização , Vacinas contra Rotavirus/administração & dosagem , Vacina contra Sarampo/administração & dosagem , Cobertura Vacinal/estatística & dados numéricos , Vacina BCG/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Feminino , Masculino , Vacinação/estatística & dados numéricos , Países em DesenvolvimentoRESUMO
OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.
Assuntos
Adjuvantes Imunológicos , Vacina BCG , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/mortalidade , Vacina BCG/uso terapêutico , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Fatores Etários , Resultado do Tratamento , Estudos Retrospectivos , Adjuvantes Imunológicos/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Administração Intravesical , Neoplasias não Músculo Invasivas da BexigaRESUMO
BackgroundsË The objective of this study was to assess the efficacy of gemcitabine as a treatment option for patients diagnosed with non-muscle invasive bladder cancer (NMIBC) who had previously experienced failure with Bacillus Calmette-Guerin (BCG) therapy in the last year. METHODS: We prospectively enrolled 28 patients with recurrent NMIBC after previous intravesical treatment in the last year who declined or were unsuitable for cystectomy between 2021 and 2023. Gemcitabine at 2,000 mg/100 mL was instilled weekly for 6 weeks. Patients were assessed for response after 8 weeks, with subsequent evaluations scheduled every three months to one year. RESULTS: The findings demonstrated that out of the 28 patients, 20 (71.4%) exhibited a complete response to intravesical gemcitabine treatment, and 8 (28.6%) had no complete response. The average age of the participants was 60.25 years. The study identified significant differences in treatment response based on age but without significant differences based on gender. Furthermore, there was no noteworthy association between tumor stage and grade and treatment response. Moreover, among patients with low-grade tumors, 66.7% achieved a complete response, while 72.7% reached a complete response among those with high-grade tumors. Of the patients who reached a complete response, 28.6% experienced no recurrence during one year of follow-up, and 42.9% developed recurrent disease within one year of treatment initiation. Ten months following treatment, a patient developed muscle-invasive bladder cancer and went on to cystectomy. CONCLUSION: In conclusion, the results suggest that intravesical gemcitabine could represent a feasible choice for NMIBC patients unresponsive to BCG therapy and ineligible for or unwilling to undergo cystectomy.
Assuntos
Antimetabólitos Antineoplásicos , Vacina BCG , Desoxicitidina , Gencitabina , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Administração Intravesical , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Seguimentos , Falha de Tratamento , Adjuvantes Imunológicos/administração & dosagem , Invasividade Neoplásica , Prognóstico , Adulto , Neoplasias não Músculo Invasivas da BexigaRESUMO
Bacille-Calmette-Guérin (BCG) is the only approved vaccine against Mycobacterium tuberculosis (MTB), offering protection not only against tuberculosis (TB) but also non-related infections. 'Trained immunity' of innate immune cells is considered one of the mechanisms of this broad protection derived through BCG. Here, we investigated the effect of BCG on Natural Killer (NK) cells, a key innate immune cell type, and their subsequent responses to mycobacterial and HIV antigens. We found that BCG-induced KLRG1+ NK cells exhibit significantly higher production of IFNγ, compared to KLRG1- cells, indicating their memory-like responses upon exposure to these antigens (p < 0.05). These findings may be important in regions of high burden of HIV and TB where BCG is routinely administered.
Assuntos
Vacina BCG , Infecções por HIV , Memória Imunológica , Interferon gama , Células Matadoras Naturais , Lectinas Tipo C , Mycobacterium tuberculosis , Receptores Imunológicos , Tuberculose , Células Matadoras Naturais/imunologia , Receptores Imunológicos/imunologia , Memória Imunológica/imunologia , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Vacina BCG/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Infecções por HIV/imunologia , Antígenos de Bactérias/imunologia , Antígenos Virais/imunologia , Imunização/métodosRESUMO
Tuberculosis (TB) is caused by infection with the bacterial pathogen Mycobacterium tuberculosis (M.tb) in the respiratory tract. There was an estimated 10.6 million people newly diagnosed with TB, and there were approximately 1.3 million deaths caused by TB in 2022. Although the global prevalence of TB has remained high for decades and is an annual leading cause of death attributed to infectious diseases, only one vaccine, Bacillus Calmette-Guérin (BCG), has been approved so far to prevent/attenuate TB disease. Correlates of protection or immunological mechanisms that are needed to control M.tb remain unknown. The protective role of antibodies after BCG vaccination has also remained largely unclear; however, recent studies have provided evidence for their involvement in protection against disease, as biomarkers for the state of infection, and as potential predictors of outcomes. Interestingly, the antibodies generated post-vaccination with BCG are linked to the activation of innate immune cascades, providing further evidence that antibody effector functions are critical for protection against respiratory pathogens such as M.tb. In this review, we aim to provide current knowledge of antibody application in TB diagnosis, prevention, and treatment. Particularly, this review will focus on 1) The role of antibodies in preventing M.tb infections through preventing Mtb adherence to epithelium, antibody-mediated phagocytosis, and antibody-mediated cellular cytotoxicity; 2) The M.tb-directed antibody response generated after vaccination and how humoral profiles with different glycosylation patterns of these antibodies are linked with protection against the disease state; and 3) How antibody-mediated immunity against M.tb can be further explored as early diagnosis biomarkers and different detection methods to combat the global M.tb burden. Broadening the paradigm of differentiated antibody profiling and antibody-based detection during TB disease progression offers new directions for diagnosis, treatment, and preventative strategies. This approach involves linking the aforementioned humoral responses with the disease state, progression, and clearance.