Human oncogenic viruses: an overview of protein biomarkers in viral cancers and their potential use in clinics.

INTRODUCTION: Although the idea that carcinogenesis might be caused by viruses was first voiced about 100 years ago, today's data disappointingly show that we have not made much progress in preventing and/or treating viral cancers in a century. According to recent studies, infections are responsible for approximately 13% of cancer development in the world. Today, it is accepted and proven by many authorities that Epstein-Barr virus (EBV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human Herpesvirus 8 (HHV8), Human T-cell Lymphotropic virus 1 (HTLV1) and highly oncogenic Human Papillomaviruses (HPVs) cause or/and contribute to cancer development in humans. AREAS COVERED: Considering the insufficient prevention and/or treatment strategies for viral cancers, in this review we present the current knowledge on protein biomarkers of oncogenic viruses. In addition, we aimed to decipher their potential for clinical use by evaluating whether the proposed biomarkers are expressed in body fluids, are druggable, and act as tumor suppressors or oncoproteins. EXPERT OPINION: Consequently, we believe that this review will shed light on researchers and provide a guide to find remarkable solutions for the prevention and/or treatment of viral cancers.

Outcomes of HTLV-1 Carriers with Diffuse Large B-Cell Lymphoma: A Single-Center Retrospective Matched Cohort Study.

BACKGROUND: The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with aggressive diseases, such as adult T-cell leukemia/lymphoma (ATLL). However, less is known on the impact of HTLV-1 infection in non-ATLL hematologic malignancies. We aimed to investigate if HTLV-1 carriers with diffuse large B-cell lymphoma (DLBCL) have worse survival outcomes than non-HTLV-1 carriers. MATERIALS AND METHODS: We performed a single-center retrospective cohort study by matching HTLV-1 carriers to non-carriers based on age, sex, Ann Arbor stage, and year of diagnosis. Our outcomes of interest were overall survival (OS) and progression-free survival (PFS). The Kaplan-Meier method was used to estimate OS and PFS between carriers and non-carriers. We fitted multivariate Cox regression models to assess the mortality and recurrence/disease progression risk of HTLV-1 infection. RESULTS: A total of 188 patients, 66 with HTLV-1 infection and 122 without HTLV-1, were included in the study. HTLV-1 carriers had higher extranodal involvement than non-carriers (47% vs. 27%, P = .010). With a median follow-up of 78 months (95% CI: 41-90 months), HTLV-1 carriers had a similar 5 year OS (41% vs. 42%, P = .940) and PFS (34% vs. 32%, P = .691) compared to non-carriers. In the multivariate Cox analysis, HTLV-1 infection was not associated with worse OS (aHR: 0.98, 95% CI: 0.64-1.50) or PFS (aHR: 0.90, 95% CI: 0.60-1.34). CONCLUSION: HTLV-1 carriers with DLBCL did not have worse survival outcomes compared to non-carriers. Our results suggest that clinicians should follow standard guidelines for DLBCL management on HTLV-1 seropositive patients.

Association between Cognitive Function and Depression with Human T-Cell Lymphotropic Virus 1 Seropositivity and Serointensity in UK Adults.

Several viral, bacterial, and parasitic diseases have been associated with cognitive function and neuropsychiatric outcomes in humans, including human T-cell lymphotropic virus 1 (HTLV-1). In this study, we sought to further generalize previously reported associations of cognitive function and depression with HTLV-1 seropositivity and serointensity using a community-based sample of adults aged approximately 40 to 70 years (mean = 55.3 years) from the United Kingdom. In this sample, the results of adjusted linear regression models showed no associations of HTLV-1 seropositivity or serointensity with reasoning, pairs-matching, or reaction-time cognitive tasks or with depression. In addition, neither age, sex, educational attainment, nor income moderated associations of HTLV-1 seropositivity or serointensity with cognitive function or depression. In this middle-aged to older middle-aged adult community sample, HTLV-1 seropositivity and serointensity do not appear to be associated with reasoning, pairs-matching, and reaction-time tasks or with depression.

Point-of-Care System for HTLV-1 Proviral Load Quantification by Digital Mediator Displacement LAMP.

This paper presents a universal point-of-care system for fully automated quantification of human T-cell lymphotropic virus type 1 (HTLV-1) proviral load, including genomic RNA, based on digital reverse RNA transcription and c-DNA amplification by MD LAMP (mediator displacement loop-mediated isothermal amplification). A disposable microfluidic LabDisk with pre-stored reagents performs automated nucleic acid extraction, reaction setup, emulsification, reverse transcription, digital DNA amplification, and quantitative fluorogenic endpoint detection with universal reporter molecules. Automated nucleic acid extraction from a suspension of HTLV-1-infected CD4+ T-lymphocytes (MT-2 cells) yielded 8 ± 7 viral nucleic acid copies per MT-2 cell, very similar to the manual reference extraction (7 ± 2 nucleic acid copies). Fully automated sample processing from whole blood spiked with MT-2 cells showed a comparable result of 7 ± 3 copies per MT-2 cell after a run time of two hours and 10 min.

Brazilian protocol for sexually transmitted infections 2020: human T-cell lymphotropic virus (HTLV) infection

Abstract This article addresses the Human T-lymphotropic virus (HTLV). This subject comprises the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. HTLV-1/2 infection is a public health problem globally, and Brazil has the largest number of individuals living with the virus. HTLV-1 causes several clinical manifestations of neoplasm (adult T-cell leukemia/lymphoma) and inflammatory nature, such as HTLV-1-associated myelopathy and other manifestations such as uveitis, arthritis, and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health authorities professionals regarding viral transmission, diagnosis, treatment, and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Bowenoid papulosis unveiling a rare cause of immunosuppression.

Bowenoid papulosis (BP) is a premalignant condition usually caused by oncogenic types of human papillomavirus (HPV) presenting clinically as warty genital papules. Adult T-cell leukaemia-lymphoma (ATLL) is a peripheral T-cell leukaemia-lymphoma caused by the retrovirus, human T-cell lymphotropic virus 1 (HTLV-1). We report a case of BP initially mistaken as genital warts; on detailed evaluation the patient had features of chronic immunosuppression. The presence of leukaemic cells in the peripheral blood, bone marrow and skin along with a positive HTLV-1 serology confirmed the diagnosis of ATLL.

Crusted (Norwegian) scabies as a strong marker of adult T-cell leukemia/lymphoma in HTLV-1 infection.

We present a rare case of crusted scabies in an human T-cell lymphotropic virus type 1 (HTLV-1) infected woman prior to onset of adult T-cell leukemia/lymphoma (ATL). We highlight the importance of this rare form of scabies as a prediagnostic sign of ATL, requiring high suspicion and monitoring of possible symptoms for early detection of ATL.

Efficacy of mirabegron for overactive bladder with human T cell lymphotropic virus-1 associated myelopathy.

OBJECTIVE: Mirabegron is widely considered as an effective and safe drug for patients with overactive bladder (OAB). However, there is no evidence regarding the efficacy of mirabegron in human T cell lymphotropic virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with OAB symptoms. The aim of the present study was to clarify the efficacy of mirabegron in HAM/TSP patients with OAB symptoms. METHODS: The present study evaluated the efficacy of mirabegron treatment (50 mg, once daily) in nineteen HAM/TSP patients with OAB symptoms by assessing subjective symptoms using the overactive bladder symptom score (OABSS) and International Prostate Symptom Score (IPSS) before and 12 weeks after administration. Voided volume (VV), maximum flow rate (Qmax ), and post-void residual (PVR) urine volume were evaluated as objective symptoms. RESULTS: Mirabegron treatment improved OABSS in terms of night-time frequency, urgency, and total score (P < .001). In addition, on the IPSS, mirabegron therapy improved urgency, nocturia, storage symptoms (Questions 2, 4 and 7 on the IPSS), as well as the total score (P < .001). The quality of life (QoL) on the IPSS also improved after treatment (P < .001). However, there were no significant changes in objective symptoms, as measured by VV, Qmax , and PVR, after treatment. One patient (5.3%) complained of dry mouth; because this adverse effect was very mild, the patient did not discontinue mirabegron. CONCLUSIONS: Mirabegron administration improved subjective symptoms in HAM/TSP patients with neurogenic OAB.

Molecular targeting for treatment of human T-lymphotropic virus type 1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases. There are conflicting reports on the efficacy of current enzyme inhibitors, mainly developed against human immunodeficiency virus (HIV), for treatment of HTLV-1 infection. New treatment approaches including monoclonal antibodies show promising results and exert significant cytotoxic effects on ATLL cells. This manuscript reviews the recent developments in molecular targeting for treatment of HTLV-1 infection.

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.

Absence of FLT3 mutations in Iranian adult T-cell leukemia/lymphoma patients.

Background: Adult T cell leukemia lymphoma (ATLL) is a rare disease, significantly linked to the infection by the human T-cell lymphotropic virus 1(HTLV-1). ATLL is typically preceded by decades of clinical latency during which infected cells accumulate selectable traits leading to a malignant transformation. Amongst all the HTLV-1 infected carriers only about 3-5% will develop ATLL. Despite the intensive attempt to improve the overall survival, ATLL remains one of worse prognosis among the hematologic malignancies. FMS like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations are mutations which are frequent among leukemic patients. We aimed to investigate the frequency of FLT3 mutation status in patients with acute type of ATLL which has not been studied yet. Methods: In this case control study 38 patients with acute type of ATLL were retrospectively analyzed between February 2015 and February 2017. Forty HTLV-1 positive patients were also used as control cases. Genomic DNA was extracted according to phenolchloroform protocol and two restriction fragment length polymorphism (RFLP) PCR reactions were set up to detect FLT3/ ITD and FLT3/TKD mutations. Differences between variables were evaluated by the chi-square test and t test for categorical and continuous variables, respectively. SPSS software v. 15 was used for statistical analysis. All P values were two sided and values less than 0.05 were considered to be significant. Results: No FLT3 mutations were detected in acute type of ATLL patients. So far, not many studies have shown the frequency of FLT3 mutation in ATLL patients Conclusion: Therefore, we conclude that although FLT3 mutations are rather unusual in the acute type of ATLL patients, but other alternative mechanisms associated with ATLL remain to be further investigated. This study was a novel project regarding the analysis of FLT3 mutation in the field of ATLL research.

Algorithm for dry eye disease diagnosis in individuals infected with human T-cell lymphotropic virus type 1 / Algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com vírus linfotrópico de células-T humanas tipo 1

ABSTRACT Purpose: To evaluate the accuracy of lacrimal film tests and propose an algorithm for the diagnosis of dry eye disease in individuals infected with human T-cell lymphotropic virus type 1. Methods: Ninety-six patients infected with human T-cell lymphotropic virus type 1 were enrolled in the study. To assess clinical complaints, patients completed the Ocular Surface Disease Index questionnaire. To evaluate lacrimal film quality, patients underwent the tear breakup time test, Schirmer I test, and Rose Bengal staining. Dry eye disease was diagnosed when at least two of the three test results were abnormal. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of the questionnaire as well as of each test alone and combined in parallel and in series were determined. Results: The most sensitive test was the tear breakup time test (98%), whereas the most specific was the Schirmer I test (100%). Rose Bengal staining had the highest overall accuracy (88.64%), whereas the Ocular Surface Disease Index had the lowest overall accuracy (62.65%). The tear breakup time test, Schirmer I test, and Ocular Surface Disease Index combined in parallel showed increased sensitivity and decreased specificity for all tests. In contrast, when combined in series, these tests demonstrated increased specificity and decreased sensitivity. Conclusion: This study shows the need to use multiple tests to evaluate tear film quality and include a symptom questionnaire as part of the diagnostic algorithm for dry eye disease.

RESUMO Objetivo: Avaliar a precisão da propedêutica do filme lacrimal e propor um algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com Vírus linfotrópico de células-T humanas tipo 1. Métodos: Noventa e seis pacientes infectados com o vírus linfotrópico de células T humana tipo 1 foram incluídos no estudo. Para avaliar sintomatologia, os pacientes responderam o questionário Índice para Doenças da Superfície Ocular. A fim de avaliar a qualidade do filme lacrimal, os pacientes foram submetidos ao teste de ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala. A doença do olho seco foi diagnosticada quando, pelo menos, dois dos testes ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala) eram anormais. Foram determinados sensibilidade, especificidade, valor preditivo positivo e negativo e acurácia do questionário e de cada teste sozinho e combinados em paralelo e em série. Resultados: O teste de ruptura do filme lacrimal foi o mais sensível (98%) e o teste de Schirmer I foi o mais específico (100%). A maior acurácia foi encontrada no teste de coloração com Rosa Bengala (88,64%), enquanto sintomas avaliados usando o questionário Índice para Doenças da Superfície Ocular teve a menor acurácia geral (62,65%). O teste de ruptura do filme lacrimal, teste de Schirmer I e Questionário de Doença da Superfície Ocular quando combinados em paralelo mostraram um aumento da sensibilidade e uma diminuição na especificidade de todos os testes. Por outro lado, combinados em série, teste de ruptura do filme lacrimal, Schirmer I e questionário Índice para Doenças da Superfície Ocular tiveram um aumento na especificidade e sensibilidade diminuída. Conclusão: Este estudo apontou a necessidade de utilizar mais do que um teste para avaliar a qualidade do filme lacrimal, bem como utilizar um questionário de sintomas como parte do algoritmo de diagnóstico para doença do olho seco.

Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1.

In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

Retroviral envelope proteins: Involvement in neuropathogenesis.

The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases. An essential prerequisite of retroviral infection is the interactions between Env (the retroviral adhesion) proteins on the virion and specific surface receptors on the host cell. These interactions facilitate fusion of the viral envelope and cellular membranes. Additional fusiogenic activities mediated by Env may be beneficial (establishment of the syncytiotrophoblast induced by a HERV-encoded Env) or detrimental to the host (syncytia formation, induction of apoptosis), and Envs are further implied in the direct induction of proinflammatory cytokines, the regulation of autophagy, and pathways of cell death. The pathogenic potential of retroviral Env is therefore not limited to the pathogenetics of infection but also comprise the pathogenic/toxic capacity of the Env protein itself.

Adult T-cell leukemia/lymphoma / Leucemia/linfoma de células T do adulto

Summary Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Twenty million people are believed to be infected throughout the world, mostly in Japan, Africa, the Caribbean, and South America, particularly in Brazil and Peru. ATL affects about 5% of infected individuals and is classified in the following clinical forms: acute, lymphoma, primary cutaneous tumoral, chronic (favorable and unfavorable), and smoldering (leukemic and non-leukemic). Although it is considered an aggressive disease, there are cases with a long progression. We emphasize the importance of clinical classification as an indispensable element for evaluating prognosis and appropriate therapeutic approach. Since several cases have been published in Brazil and this disease is still poorly known, we decided to make a review paper for dissemination of clinical, hematological and pathological aspects, diagnosis, and therapy. The best way to reduce the occurrence of ATL would be halting the transmission of the virus through breastfeeding.

Resumo A leucemia/linfoma de células T do adulto (LLcTA) é uma neoplasia de células T maduras CD4+ causada pelo vírus linfotrópico para células T humanas tipo 1 (HTLV-1). Acredita-se que existem cerca de 20 milhões de pessoas infectadas em todo o mundo, principalmente no Japão, na África, no Caribe e na América do Sul, particularmen te no Brasil e no Peru. A LLcTA acomete cerca de 5% dos indivíduos infectados e classifica-se nas seguintes formas clínicas: aguda, linfomatosa, tumoral primária de pele, crônica (favorável e desfavorável) e indolente (leucêmica e não leucêmica). Embora seja considerada uma doença agressiva, há casos com longa evolução. Salientamos a importância da classificação clínica como elemento im prescindível para avaliação do prognóstico e conduta terapêutica adequada. Como já foram publicados vários casos no Brasil e essa doença ainda é pouco conhecida, decidimos fazer um trabalho de revisão para divulgar os seus aspectos clínicos, hematológicos, anatomopatológi cos, diagnósticos e terapêuticos. O melhor meio de redu zir a ocorrência de LLcTA seria sustando a transmissão vertical do vírus pela amamentação.

Seroprevalencia de HTLV1/2 en donantes de sangre, Boyacá - Colombia, 2011-2013 / Seroprevalence 1/2 HTLV in blood donors in Boyacá - Colombia between 2011 and 2013

Introducción: El virus linfotrópico humano de células T es un retrovirus, se encuentra asociado al riesgo de presentar dermatitis infecciosa, uveítis, polimiositis, artropatías, paraparesia espástica tropical, linfoma de células T del adulto y mieloma. Una de las vías de transmisión del HTLV 1/2 es la transfusión sanguínea de unidades que contienen el virus. Para evitar la transmisión de la infección por este retrovirus, el tamizaje en muestras de donantes de sangre ha sido obligatorio en muchos países y más recientemente en Colombia. Objetivo: Reportar la seroprevalencia de virus HTLV 1/ 2 en donantes de sangre de Boyacá-Colombia entre los años 2011 a 2013. Materiales y Métodos: Estudio descriptivo retrospectivo, en el que se estableció la seroprevalencia de HTLV 1/2 en 48.782 donantes de sangre captados en el departamento de Boyacá por tres bancos de sangre, utilizando la técnica quimioluminiscencia y como pruebas confirmatorias la técnica de InmunoBlot. Resultados: De los donantes tamizados, el 0,23% (113/48.782) fueron serorreactivos (positivos en la prueba de quimioluminiscencia), el 0,16% (78/48.782) fueron negativos, un 0,04% (21/48.782) fueron indeterminados y el 0,03% (14/48.782) fueron seropositivos por la técnica de InmunoBlot. Los donantes seropositivos correspondieron según el sexo a 0,016% (8/48.782) mujeres y 0,012% (6/48.782) a hombres. Conclusión: La prevalencia de HTLV 1/2 fue de 0,03%, similar a la de la mayoría de países que cuentan con reporte de esta determinación en donantes de sangre. Los datos generados en el estudio son los primeros reportados para Boyacá y aportan a la epidemiología del virus a nivel nacional.

Introduction: The Human T-cell lymphotropic virus is a retrovirus found to be associated with risks of infectious dermatitis, uveitis, polymyositis, arthropathies, tropical spastic paraparesis, myeloma and T-cell lymphoma. One of the means of transmission of HTLV 1/2 is the transfusion of blood units contaminated by the virus. To prevent this kind of transmission, blood donor screening has recently become a standard in Colombia and in many other countries. Objective: To report the seroprevalence of HTLV 1/2 virus in blood donors from Boyacá between 2011 and 2013. Materials and Methods: A retrospective descriptive study was performed, in which the seroprevalence of HTLV 1/2 was established in 48,782 blood donors from three blood banks in the department of Boyacá by using both chemiluminescence and western blot techniques. Results: From the screened donors, 0.23% (113 / 48,782) were seroreactive (chemiluminescence positive), 0.16% (78 / 48,782) were negative, 0.04% (21 / 48,782) were undefined and 0.03% (14 / 48,782) were seropositive by western blot. Concerning gender, seropositive donors were 0.016% (8/48,782) female and 0.012% (6 / 48,782) male. Conclusion: The prevalence of HTLV 1/2 was 0.03% which is similar to what has been found in most of the countries. The data generated in this study is the first of this kind available for Boyacá and will likely contribute to the virus epidemiology at the national level.

CD160 expression defines a uniquely exhausted subset of T lymphocytes in HTLV-1 infection.

HTLV-1 infection is a life-long retroviral infection. Chronic viral antigenic stimulation induces persistent infection which results in a clinically asymptomatic carrier state. Only a minor proportion of infected individuals develop adult T cell leukemia/lymphoma (ATLL) or HTLV-1-associated myelopathy/tropical spastic myelopathy (HAM/TSP). This is dependent on a balance of host and genetic factors. CD8+ cytotoxic T lymphocyte function is important in the immune response against viral infection; however, the contribution of CD160 receptor associated with CD8+ T lymphocytes is unclear. Thus, we sought to decipher its role on CTL function in HTLV-1 infection. Here, we report high frequencies of CD160 on CD8+ T cells, with significantly higher levels on HTLV-1 specific CD8+ T cells. Intercepting the CD160 pathway via blockade of the receptor or its ligand, herpes virus entry mediator (HVEM) resulted in improved perforin production and CD107a degranulation of HTLV-1 specific CD8+ T cells. Analysis of the CD160-expressing CD8+ cells demonstrated a unique subset associated with a highly differentiated effector memory based on CD45RA and CCR7 co-expression, increased expression of inhibitory molecules, 2B4 and PD1. Altogether, these results suggest a role for CD160/HVEM pathway in regulating immune response against HTLV-1 infection which may prove promising in the development of immune therapies for the treatment of HTLV-1 infection and other associated disorders.

Evolving Therapy of Peripheral T-cell Lymphoma: 2010 and beyond.

The peripheral T-cell lymphomas are a rare, heterogeneous group of non-Hodgkin's lymphomas which have an aggressive clinical course. Treatment approaches have traditionally been similar to those of diffuse large B-cell lymphomas, but outcomes have been inferior. Novel approaches involving agents and pathways developed from a better understanding of the biology of the diseases have led to therapeutic advances. The introduction of new agents, including antifolates, immunoconjugates, histone deacetylase inhibitors, monoclonal antibodies, nucleoside analogs, proteasome inhibitors, and signaling inhibitors have improved outcomes for patients with relapsed and refractory disease and are being incorporated into strategies for first-line therapy. Stem cell transplantation remains a potentially curative option for a subset of patients.