RESUMEN
A primary challenge in lentiviral gene therapy of ß-hemoglobinopathies is to maintain low vector copy numbers to avoid genotoxicity while being reliably therapeutic for all genotypes. We designed a high-titer lentiviral vector, LVß-shα2, that allows coordinated expression of the therapeutic ßA-T87Q-globin gene and of an intron-embedded miR-30-based short hairpin RNA (shRNA) selectively targeting the α2-globin mRNA. Our approach was guided by the knowledge that moderate reduction of α-globin chain synthesis ameliorates disease severity in ß-thalassemia. We demonstrate that LVß-shα2 reduces α2-globin mRNA expression in erythroid cells while keeping α1-globin mRNA levels unchanged and ßA-T87Q-globin gene expression identical to the parent vector. Compared with the first ßA-T87Q-globin lentiviral vector that has received conditional marketing authorization, BB305, LVß-shα2 shows 1.7-fold greater potency to improve α/ß ratios. It may thus result in greater therapeutic efficacy and reliability for the most severe types of ß-thalassemia and provide an improved benefit/risk ratio regardless of the ß-thalassemia genotype.
Asunto(s)
Vectores Genéticos/administración & dosificación , ARN Interferente Pequeño/genética , Globinas alfa/genética , Globinas beta/genética , Talasemia beta/genética , Línea Celular , Células Cultivadas , Regulación hacia Abajo , Células Eritroides/citología , Células Eritroides/metabolismo , Genotipo , Humanos , Células K562 , Lentivirus/genética , Lentivirus/fisiología , MicroARNs/antagonistas & inhibidores , Cultivo Primario de Células , Carga Viral , Talasemia beta/terapiaRESUMEN
Coronavirus disease 2019 (COVID-19) infection in patients with haematological neoplasms has been associated with increased mortality; however, many studies in this patient group were reported early in the pandemic. The authors evaluated outcomes of COVID-19 infection in patients with haematological conditions following widespread vaccination, newer viral variants and increasingly effective antiviral therapies. A 4% mortality rate was found and contemporary risk factors for hospitalisation including older age, nonvaccination or partial COVID-19 vaccination status and infection with non-Omicron strain were identified.
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COVID-19 , Neoplasias Hematológicas , Hematología , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , Neoplasias Hematológicas/terapiaRESUMEN
Beta-thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression is reduced resulting in increased iron absorption and primary iron overload. Hepcidin is under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage of haemojuvelin (HJV), a co-receptor for the bone morphogenetic protein (BMP)-mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering the central role of the TMPRSS6/HJV/hepcidin axis in iron homeostasis, the inhibition of TMPRSS6 expression represents a promising therapeutic strategy to increase hepcidin production and ameliorate anaemia and iron overload in ß-thalassaemia. In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of Tmprss6 (SLN124) in ß-thalassaemia mice (Hbbth3/+ ). Two subcutaneous injections of SLN124 (3 mg/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly. Treatment with the iron chelator, deferiprone (DFP), did not impact any of the erythroid parameters. However, the combination of SLN124 with DFP was more effective in reducing hepatic iron overload than either treatment alone. Collectively, we show that the combination therapy can ameliorate several disease symptoms associated with chronic anaemia and iron overload, and therefore represents a promising pharmacological modality for the treatment of ß-thalassaemia and related disorders.
Asunto(s)
Deferiprona/uso terapéutico , Eritropoyesis/efectos de los fármacos , Hepcidinas/biosíntesis , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/prevención & control , Proteínas de la Membrana/antagonistas & inhibidores , ARN Interferente Pequeño/uso terapéutico , Talasemia beta/tratamiento farmacológico , Acetilgalactosamina/administración & dosificación , Animales , Deferiprona/administración & dosificación , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Perfilación de la Expresión Génica , Hepcidinas/genética , Humanos , Hierro/sangre , Quelantes del Hierro/administración & dosificación , Sobrecarga de Hierro/etiología , Hígado/metabolismo , Magnesio/metabolismo , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Interferencia de ARN , ARN Interferente Pequeño/administración & dosificación , Especies Reactivas de Oxígeno , Serina Endopeptidasas/genética , Bazo/metabolismo , Bazo/ultraestructura , Zinc/metabolismo , Talasemia beta/complicaciones , Talasemia beta/metabolismo , Talasemia beta/fisiopatologíaRESUMEN
Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.
Asunto(s)
Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Hematología , Australia/epidemiología , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Humanos , Saccharomyces cerevisiaeRESUMEN
BACKGROUND: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There are minimal data on HT in the Australian setting. AIMS: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. METHODS: All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed using the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. RESULTS: A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score ≥3). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) induction was used in 69%, with an overall response rate of 82% (complete response (CR), 75%). Sixty-one percent of these induction responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs 54%, P = 0.057) and 5-year OS (82% vs 46%, P = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction responders. CONCLUSIONS: Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naïve at HT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia/epidemiología , Ciclofosfamida , Supervivencia sin Enfermedad , Doxorrubicina , Humanos , Recurrencia Local de Neoplasia , Prednisona , Rituximab , Trasplante Autólogo , VincristinaRESUMEN
Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. This was not dependent on reduction of the IRF4-MYC "axis," as neither protein was consistently downregulated, despite cell death occurring, and overexpression of either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos repress the expression of interferon-stimulated genes (ISGs), including CD38, and their loss led to the activation of an interferon-like response, contributing to MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of Ikaros or treatment with interferon resulted in an upregulation of CD38 surface expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody-dependent cellular cytotoxicity. These results give further insight into the mechanism of action of the IMiDs and provide mechanistic rationale for combination with anti-CD38 monoclonal antibodies.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Sistemas CRISPR-Cas , Factor de Transcripción Ikaros/genética , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , HumanosRESUMEN
AIMS: An indolent T-lymphoblastic proliferation (iT-LBP) is a benign, reactive expansion of immature terminal deoxynucleotidyl transferase (TdT)-positive T cells found in extrathymic tissues. iT-LBP can be challenging to distinguish from malignant processes, specifically T-lymphoblastic lymphoma (T-LBL), given the overlapping clinical and histological features. Recently, it has been shown that LIM domain only 2 (LMO2) is overexpressed in T-LBL but not in reactive immature TdT+ T cells in the thymus. On the basis of these findings, the aim of this study was to investigate the expression of LMO2 by using immunohistochemistry and its role in differentiating iT-LBPs from T-LBLs. METHODS AND RESULTS: We retrospectively identified cases of iT-LBP and T-LBL from the pathology archives of four institutions. Seven iT-LBP cases (including five new cases that have not been reported in the literature) and 13 T-LBL cases were analysed. Clinical, morphological, immunophenotypic and molecular data were analysed. Immunohistochemical staining with LMO2 was performed on all iT-LBP and T-LBL cases. A review of five new iT-LBP cases showed similar morphological, immunophenotypic and molecular features to those of previously reported cases. All iT-LBP cases were negative for LMO2 (0/7), whereas 92% of T-LBL cases (12/13) expressed LMO2; the sensitivity was 92% (confidence interval 64-100%) and the specificity was 100% (confidence interval 59-100%). CONCLUSION: We confirm previously published findings that iT-LBP cases show highly overlapping morphological and immunophenotypic features with T-LBL. Importantly, LMO2 expression is a sensitive and specific marker with which to rule out iT-LBP.
Asunto(s)
Proteínas con Dominio LIM/metabolismo , Linfoma de Células T , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/patología , Inmunohistoquímica , Linfoma de Células T/diagnóstico , Linfoma de Células T/patología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Estudios RetrospectivosRESUMEN
Antibody-secreting cells (ASCs) are critical for a functional and effective adaptive immune system. In a number of illnesses, however, these same cells contribute to the underlying disease state leading to significant morbidity and mortality. While therapeutic targeting of antibody-secreting cells has progressed significantly over the last two decades, many of these conditions remain major health problems. In this review, we will discuss current and potential therapeutic targeting of ASCs in the context of the known biology of these cells.
Asunto(s)
Células Productoras de Anticuerpos/inmunología , Células Productoras de Anticuerpos/metabolismo , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Animales , Formación de Anticuerpos , Células Productoras de Anticuerpos/citología , Células Productoras de Anticuerpos/efectos de los fármacos , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Supervivencia Celular/genética , Supervivencia Celular/inmunología , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Humanos , Terapia Molecular Dirigida , Fenotipo , Células Plasmáticas/citología , Células Plasmáticas/efectos de los fármacos , Transcripción GenéticaRESUMEN
Iron deficiency and iron deficiency anaemia remain prevalent in Australia. The groups at highest risk are pre-menopausal women, socially disadvantaged people and those of Indigenous background. Diagnosing iron deficiency using a full blood examination and iron studies can be difficult and can be further complicated by concomitant inflammation. Results of iron studies should always be interpreted as an overall picture rather than focusing on individual parameters. In difficult clinical scenarios, soluble transferrin receptor assays can be useful. Management of iron deficiency involves identification and treatment of the cause of iron deficiency, as well as effective iron replacement. Clinicians should always take a detailed history and perform a comprehensive physical examination of a patient with iron deficiency. Patients should be monitored even if a likely cause of iron deficiency is identified. Patients who fail to respond to iron replacement or maintain iron status should be referred for further investigation, including endoscopy to exclude internal bleeding. Both enteral and parenteral iron are effective at replacing iron. For most adult patients, we recommend trialling daily oral iron (30-100 mg of elemental iron) as the first-line therapy. Safety and efficacy of intravenous iron infusions have improved with the availability of a newer formulation, ferric carboxymaltose. Patients who fail to respond to oral iron replacement can be safely managed with intravenous iron. Blood transfusion for iron deficiency anaemia should be reserved for life-threatening situations and should always be followed by appropriate iron replacement.
Asunto(s)
Anemia Ferropénica/epidemiología , Anemia Ferropénica/terapia , Compuestos Férricos/administración & dosificación , Hierro/sangre , Maltosa/análogos & derivados , Administración Oral , Anemia Ferropénica/etiología , Australia/epidemiología , Transfusión Sanguínea , Médula Ósea/patología , Niño , Femenino , Compuestos Férricos/efectos adversos , Humanos , Infusiones Intravenosas , Hierro/administración & dosificación , Deficiencias de Hierro , Maltosa/administración & dosificación , Maltosa/efectos adversos , EmbarazoAsunto(s)
COVID-19 , Mieloma Múltiple , Personal de Salud , Humanos , Mieloma Múltiple/diagnóstico , SARS-CoV-2RESUMEN
Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM. While treatment of WM has often been considered together with other indolent B cell lymphomas, there are unique aspects of WM management that require specific care. These include the unreliability of IgM and paraprotein measurements in monitoring patients prior to and after treatment, the lack of correlation between disease burden and symptoms and rituximab-induced IgM flare. Moreover, while bendamustine and rituximab has recently been approved for reimbursed frontline use in WM in Australia, other regimens, including ibrutinib- and bortezomib-based treatments, are not funded, requiring tailoring of treatment to the regional regulatory environment. The Medical and Scientific Advisory Group of the Myeloma Foundation Australia has therefore developed clinical practice guidelines with specific recommendations for the work-up and therapy of WM to assist Australian clinicians in the management of this disease.
Asunto(s)
Antineoplásicos/uso terapéutico , Inmunoglobulina M/sangre , Macroglobulinemia de Waldenström/tratamiento farmacológico , Adenina/análogos & derivados , Comités Consultivos , Australia , Clorhidrato de Bendamustina/uso terapéutico , Médula Ósea/patología , Bortezomib/uso terapéutico , Humanos , Mutación , Factor 88 de Diferenciación Mieloide/genética , Piperidinas , Células Plasmáticas/patología , Guías de Práctica Clínica como Asunto , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Rituximab/uso terapéutico , Sociedades Médicas , Macroglobulinemia de Waldenström/diagnósticoRESUMEN
The role of specific members of the NF-κB family of transcription factors in CD8 T-cell selection and development is largely unknown. Here, we show that mice lacking NF-κB1 develop a unique population of conventional CD8 single-positive (SP) thymocytes with memory T cell-like properties that populate peripheral immune organs. Development of this memory-like population is not due to PLZF(+) thymocytes and instead coincides with changes in CD8 T-cell selection. These include a reduction in the efficiency of negative selection and a dependence on MHC class Ia or Ib expressed by haematopoietic cells. These findings indicate that NF-κB1 regulates multiple events in the thymus that collectively inhibit the excess development of CD8(+) thymocytes with memory cell characteristics.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica/fisiología , FN-kappa B/fisiología , Timo/citología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Inmunofenotipificación , Interleucina-4/biosíntesis , FN-kappa B/genética , Transducción de SeñalRESUMEN
BACKGROUND: Demand for platelet (PLT) and plasma transfusions is increasing. Improved clinical supply and contingency planning requires greater understanding of usage profiles and urgency of clinical requirement. STUDY DESIGN AND METHODS: This study was a random-sample survey of PLT and plasma units produced in Victoria, Australia, to determine product disposition, recipient demographics, clinical indications for transfusion, and urgency (or "deferability") of need. PLTs and fresh-frozen plasma (FFP) were tagged with a case report form before distribution. RESULTS: A total of 1252 PLT and 1837 FFP units were tagged, comprising 8.3 and 13.3% of all products issued during the study period. The fate of 1243 PLT and 1808 FFP units was determined. Of products issued, 72.2% of PLTs and 87.8% of FFP were transfused. Hematologic and oncologic disorders accounted for 63.9% of PLT transfusions, with acute myeloid leukemia alone accounting for 26%. Conversely, surgical patients received the largest proportion of FFP (40.4%), predominantly for cardiothoracic, solid organ transplant, and vascular surgery. Approximately 15% of PLT transfusions and 35% of plasma transfusions were required within 1 hour, and 80% of PLT transfusions and 90% of FFP transfusions were required within 24 hours. Wastage rates were higher in regional blood banks. CONCLUSION: The PUPPY study is a comprehensive and detailed population-based assessment of PLT and plasma usage, including urgency of use. It identifies specific clinical areas with high demand for PLT and FFP transfusion and demonstrates the high urgency of need for both products. These data inform clinical supply and contingency planning activities.
Asunto(s)
Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Plaquetas , Técnicas de Planificación , Plasma , Bancos de Sangre/normas , Enfermedades Hematológicas/terapia , Humanos , Neoplasias/terapia , Procedimientos Quirúrgicos Operativos , Encuestas y Cuestionarios , Almacenamiento de Sangre/métodosRESUMEN
Although the diverse functions served by the nuclear factor-κB (NF-κB) pathway in virtually all cell types are typically employed to deal with stress responses, NF-κB transcription factors also play key roles in the development of hemopoietic cells. This review focuses on how NF-κB transcription factors control various aspects of thymic T-cell and myeloid cell differentiation that include its roles in hemopoietic precursors, conventional αß T cells, CD4(+) regulatory T cells, natural killer T cells, γδ T cells, macrophages, and dendritic cells.
Asunto(s)
Hematopoyesis/fisiología , FN-kappa B/química , FN-kappa B/metabolismo , Subunidades de Proteína/metabolismo , Animales , Linaje de la Célula , Humanos , Células Mieloides/metabolismo , Linfocitos T/metabolismo , Timocitos/metabolismoRESUMEN
The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.
Asunto(s)
Anemia Aplásica/genética , Benzoatos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Quelantes del Hierro/farmacología , Síndromes Mielodisplásicos/genética , FN-kappa B/antagonistas & inhibidores , Transcripción Genética/efectos de los fármacos , Triazoles/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis , Anemia Aplásica/tratamiento farmacológico , Animales , Benzoatos/uso terapéutico , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Línea Celular , Células Cultivadas , Deferasirox , Deferoxamina/farmacología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Síndromes Mielodisplásicos/tratamiento farmacológico , ARN Largo no Codificante , Triazoles/uso terapéutico , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bortezomib/administración & dosificación , Linfoma Plasmablástico/tratamiento farmacológico , Linfoma Plasmablástico/mortalidad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfoma Plasmablástico/patología , Prednisona/administración & dosificación , Prednisona/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
α-Thalassemia represents one of the most important genetic modulators of ß-hemoglobinopathies. During this last decade, the ongoing interest in characterizing genotype-phenotype relationships has yielded incredible insights into α-globin gene regulation and its impact on ß-hemoglobinopathies. In this review, we provide a holistic update on α-globin gene expression stemming from DNA to RNA to protein, as well as epigenetic mechanisms that can impact gene expression and potentially influence phenotypic outcomes. Here, we highlight defined α-globin targeted strategies and rationalize the use of distinct molecular targets based on the restoration of balanced α/ß-like globin chain synthesis. Considering the therapies that either increase ß-globin synthesis or reactivate γ-globin gene expression, the modulation of α-globin chains as a disease modifier for ß-hemoglobinopathies still remains largely uncharted in clinical studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Bortezomib/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Regulatory T cells (Tregs) are a specialized subset of CD4 T cells that have an indispensable role in maintaining immune homeostasis and tolerance. Although studies in mice and humans have clearly highlighted that the absence of these cells results in severe autoimmunity and inflammation, increased Treg numbers and/or function is not always beneficial. This is best exemplified in certain cancers where increased Tregs promote cancer progression by interfering with immune surveillance. Conversely, in other types of cancers that have an inflammatory component, Tregs can inhibit cancer progression by dampening inflammation. In this review article, we provide a historical perspective of the discovery of Tregs, followed by a summary of the existing literature on the role of Tregs in malignancy.