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1.
Histopathology ; 78(1): 187-214, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33382495

RESUMO

Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.

2.
Cancers (Basel) ; 12(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260897

RESUMO

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary T-cell lymphoma of the digestive tract derived from intraepithelial lymphocytes and characterized by an aggressive clinical course. In this study, nine cases of Japanese MEITL were analyzed by targeted Next Generation Sequencing (NGS) and immunohistochemistry and were integrated with previously reported whole-genome copy number microarray-based assay data. The highlight of our findings is that all cases showed alterations of the tumor suppressor gene SETD2 by mutations and/or loss of the corresponding 3p21 locus. We also demonstrated that all cases showed mutations in one or more genes of JAK/STAT pathway. Therefore, the combination of epigenetic deregulation and cell signaling activation represent major oncogenic events in the pathogenesis of MEITL in Asian MEITL, similar to Western MEITL.

3.
Blood ; 136(25): 2848-2849, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331930
4.
Swiss Med Wkly ; 150: w20387, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33181855

RESUMO

A 22-year-old male with a typical history of pauci-symptomatic COVID-19 3 weeks earlier, confirmed by positive serology for SARS-CoV-2 (IgG), was admitted to the intensive care unit because of severe myocarditis with refractory cardiogenic shock that required extracorporeal life support. Due to a clinical presentation suggestive of Kawasaki-like disease with coronary aneurysm and severe systemic inflammation, intravenous immunoglobulins were administered in combination with tocilizumab. The initial clinical course was favourable with these treatments. However, the patient subsequently developed a severe mononeuritis multiplex leading to bilateral foot drop, which required intensive immunosuppressive therapy (corticosteroids, cyclophosphamide and rituximab). The clinical presentation meets the criteria for multisystem inflammatory syndrome associated with SARS-CoV-2, but includes very severe organ damages. Early recognition, a multidisciplinary approach and aggressive therapeutic intervention can lead to a favourable outcome.

5.
Front Oncol ; 10: 1745, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042818

RESUMO

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.

6.
Hemasphere ; 4(5): e461, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33062943

RESUMO

Peripheral T-cell lymphomas are a heterogeneous group of rare diseases with an aggressive behavior and dismal prognosis. Their classification is complex and still evolving, and several biomolecular markers now help refine the prognosis of specific disease entities, although still have limited impact in tailoring the treatment. First-line treatment strategies can cure only a minority of patients and relapsed-refractory disease still represents the major cause of failure. Frontline autologous transplantation may have an impact in the consolidation of response; however, its role is still questioned as far as complete responses obtained after induction chemotherapy are concerned. Newer drugs are now being evaluated in clinical trials, but effective salvage strategies for those who experience treatment failures are lacking. Here we review and discuss the most controversial aspects of diagnosis and treatment of peripheral T-cell lymphomas.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33071956

RESUMO

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called "red-to-yellow" transition. Following hematopoietic recovery, such as upon BM transplantation, a "yellow-to-red" transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-µCT) upon osmium-tetroxide lipid staining. Due to user-dependent variables, reproducibility in longitudinal studies is a challenge for both methods. Here we report the development of a semi-automated image analysis plug-in, MarrowQuant, which employs the open-source software QuPath, to systematically quantify multiple bone components in H&E sections in an unbiased manner. MarrowQuant discerns and quantifies the areas occupied by bone, adipocyte ghosts, hematopoietic cells, and the interstitial/microvascular compartment. A separate feature, AdipoQuant, fragments adipocyte ghosts in H&E-stained sections of extramedullary adipose tissue to render adipocyte area and size distribution. Quantification of BM hematopoietic cellularity with MarrowQuant lies within the range of scoring by four independent pathologists, while quantification of the total adipocyte area in whole bone sections compares with volumetric measurements. Employing our tool, we were able to develop a standardized map of BM hematopoietic cellularity and adiposity in mid-sections of murine C57BL/6 bones in homeostatic conditions, including quantification of the highly predictable red-to-yellow transitions in the proximal section of the caudal tail and in the proximal-to-distal tibia. Additionally, we present a comparative skeletal map induced by lethal irradiation, with longitudinal quantification of the "red-to-yellow-to-red" transition over 2 months in C57BL/6 femurs and tibiae. We find that, following BM transplantation, BM adiposity inversely correlates with kinetics of hematopoietic recovery and that a proximal to distal gradient is conserved. Analysis of in vivo recovery through magnetic resonance imaging (MRI) reveals comparable kinetics. On human trephine biopsies MarrowQuant successfully recognizes the BM compartments, opening avenues for its application in experimental, or clinical contexts that require standardized human BM evaluation.

9.
Front Oncol ; 10: 1439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923397

RESUMO

The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and laboratory suites require same day consolidation of all procedures. With laboratory medicine absorbed by the need to deploy large scale COVID-testing, the availability of routine molecular tests is affected. Finally, we are increasingly faced with the challenge of making complex treatment decisions in SARS-CoV-2 positive patients with aggressive but potentially curable blood cancers. When to treat, how to treat, when to wait, how long to wait, how to predict and manage toxicities, and how to avoid compromising cure rates remains unknown. We present an outline of the scientific, medical, and operational challenges posed by the COVID-19 pandemic at selected American and European institutions and offer our current view of the key elements of a response. While the peak of the pandemic may be past us, in the absence of a vaccine risks remain, and our alertness and response to future challenges need to be refined and consolidated.

10.
J Crohns Colitis ; 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32920643

RESUMO

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.

11.
Virchows Arch ; 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32696224

RESUMO

Natural killer (NK)-cell enteropathy (NKCE) and lymphomatoid gastropathy (LG) are closely related lymphoproliferative disorders (LPDs) composed of mature and Epstein-Barr virus (EBV)-negative NK-cells. Although these uncommon and indolent lymphoid proliferations mostly arise within the gastrointestinal (GI) tract as their designations implies, a few cases have been reported outside the GI tract. We hereby describe a unique case of lymph node infiltration by such EBV-negative NK-cell proliferation fortuitously found during routine examination of a gallbladder resected for biliary lithiasis. The histologic, phenotypic, and molecular features of this NK-cell proliferation, which were very similar if not identical to those previously reported in NKCE or LG, suggest that similar indolent EBV-negative NK-cell LPDs may also occasionally involve lymph nodes.

12.
Cancer J ; 26(3): 176-185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32496451

RESUMO

Twenty-five years after the Revised European American Classification of Lymphoid Neoplasms classification was published, its principle of an integrative approach to disease definition based on several parameters still prevails and has been adopted and expanded in the following World Health Organization classifications of tumors of the hematopoietic organs. The latest World Health Organization classification revised in 2017 comprises more than 80 entities of mature lymphoid neoplasms (B-cell, T-cell, and Hodgkin lymphomas), which are defined according to their morphology, immunophenotype, genetic lesions and molecular profiles, clinical features, and cellular derivation. The classification also recognizes both incipient and indolent lymphoid neoplasms with a low potential of progression. In this review, we highlight some of the new data and recent modifications introduced in the 2017 classification.

13.
Nat Commun ; 11(1): 2465, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424289

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD+ LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD+ B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+ DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD+ BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.


Assuntos
Antígenos de Bactérias/imunologia , Linfócitos B/imunologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/microbiologia , Moraxella catarrhalis/imunologia , Adolescente , Adulto , Idoso , Autoantígenos/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Criança , RNA Polimerases Dirigidas por DNA/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Doença de Hodgkin/sangue , Humanos , Imunoglobulina D/metabolismo , Fragmentos Fab das Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Receptores de Antígenos de Linfócitos B/metabolismo
14.
JAMA Oncol ; 6(2): 291-292, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31944223
15.
Haematologica ; 105(7): 1895-1906, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31558678

RESUMO

Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4+ (n=4), CD8+ (n=4), CD4+/CD8+ (n=1) and CD4-/CD8- (n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) of these lymphoproliferative disorders. The CD4+, CD4+/CD8+, and CD4-/CD8- cases harbored frequent alterations of JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8+ cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case was a harbinger of disease transformation. The CD4+ and CD4+/CD8+ lymphoproliferative disorders displayed heterogeneous Th1 (T-bet+), Th2 (GATA3+) or hybrid Th1/Th2 (T-bet+/GATA3+) profiles, while the majority of CD8+ disorders and the CD4-/CD8- disease showed a type-2 polarized (GATA3+) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8+ cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and confirm the heterogeneous nature of these diseases. Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases.

16.
Pathology ; 52(1): 78-99, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785821

RESUMO

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of uncommon malignancies derived from mature T cells and usually characterised by an aggressive clinical course. Their clinical presentation, localisation and pattern of dissemination are highly variable, but the majority of cases present as nodal diseases. The recently revised classification of lymphomas has incorporated many new molecular genetic data derived from gene expression profiling and next generation sequencing studies, which refine the definition and diagnostic criteria of several entities. Nevertheless, the distinction of PTCL from various reactive conditions, and the diagnosis of PTCL subtypes remains notably challenging. Here, an updated summary of the clinicopathological and molecular features of the most common nodal-based PTCLs (angioimmunoblastic T-cell lymphoma and other nodal lymphomas derived from follicular T helper cells, anaplastic large cell lymphomas and peripheral T-cell lymphoma, not otherwise specified) is presented. Practical recommendations in the diagnostic approach to nodal T-cell lymphoproliferations are presented, including indications for the appropriate use and interpretation of ancillary studies. Finally, we discuss commonly encountered diagnostic problems, including pitfalls and mimics in the differential diagnosis with various reactive conditions, and the criteria that allow proper identification of distinct PTCL entities.


Assuntos
Expressão Gênica/fisiologia , Linfoma Anaplásico de Células Grandes/patologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T/patologia , Diagnóstico Diferencial , Perfilação da Expressão Gênica/métodos , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma de Células T/diagnóstico , Linfoma de Células T Periférico/genética
17.
Haematologica ; 105(6): 1582-1592, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31488561

RESUMO

Peripheral T-cell lymphoma comprises a heterogeneous group of mature non-Hodgkin lymphomas. Their diagnosis is challenging, with up to 30% of cases remaining unclassifiable and referred to as "not otherwise specified". We developed a reverse transcriptase-multiplex ligation-dependent probe amplification gene expression profiling assay to differentiate the main T-cell lymphoma entities and to study the heterogeneity of the "not specified" category. The test evaluates the expression of 20 genes, including 17 markers relevant to T-cell immunology and lymphoma biopathology, one Epstein-Barr virus-related transcript, and variants of RHOA (G17V) and IDH2 (R172K/T). By unsupervised hierarchical clustering, our assay accurately identified 21 of 21 ALK-positive anaplastic large cell lymphomas, 16 of 16 extranodal natural killer (NK)/T-cell lymphomas, 6 of 6 hepatosplenic T-cell lymphomas, and 13 of 13 adult T-cell leukemia/lymphomas. ALK-negative anaplastic lymphomas (n=34) segregated into one cytotoxic cluster (n=10) and one non-cytotoxic cluster expressing Th2 markers (n=24) and enriched in DUSP22-rearranged cases. The 63 TFH-derived lymphomas divided into two subgroups according to a predominant TFH (n=50) or an enrichment in Th2 (n=13) signatures. We next developed a support vector machine predictor which attributed a molecular class to 27 of 77 not specified T-cell lymphomas: 17 TFH, five cytotoxic ALK-negative anaplastic and five NK/T-cell lymphomas. Among the remaining cases, we identified two cell-of-origin subgroups corresponding to cytotoxic/Th1 (n=19) and Th2 (n=24) signatures. A reproducibility test on 40 cases yielded a 90% concordance between three independent laboratories. This study demonstrates the applicability of a simple gene expression assay for the classification of peripheral T-cell lymphomas. Its applicability to routinely-fixed samples makes it an attractive adjunct in diagnostic practice.

19.
Blood ; 134(24): 2159-2170, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31562134

RESUMO

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell malignancies; approximately one-third of cases are designated as PTCL-not otherwise specified (PTCL-NOS). Using gene-expression profiling (GEP), we have previously defined 2 major molecular subtypes of PTCL-NOS, PTCL-GATA3 and PTCL-TBX21, which have distinct biological differences in oncogenic pathways and prognosis. In the current study, we generated an immunohistochemistry (IHC) algorithm to identify the 2 subtypes in paraffin tissue using antibodies to key transcriptional factors (GATA3 and TBX21) and their target proteins (CCR4 and CXCR3). In a training cohort of 49 cases of PTCL-NOS with corresponding GEP data, the 2 subtypes identified by the IHC algorithm matched the GEP results with high sensitivity (85%) and showed a significant difference in overall survival (OS) (P = .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n = 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P = .003). In multivariate analysis, a high International Prognostic Index score (3-5) and the PTCL-GATA3 subtype identified by IHC were independent adverse predictors of OS (P = .0015). Additionally, the 2 IHC-defined subtypes were significantly associated with distinct morphological features (P < .001), and there was a significant enrichment of an activated CD8+ cytotoxic phenotype in the PTCL-TBX21 subtype (P = .03). The IHC algorithm will aid in identifying the 2 subtypes in clinical practice, which will aid the future clinical management of patients and facilitate risk stratification in clinical trials.


Assuntos
Biomarcadores Tumorais , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Adulto , Idoso , Algoritmos , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes
20.
PLoS Pathog ; 15(7): e1007918, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329640

RESUMO

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers.


Assuntos
Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Receptor de Morte Celular Programada 1/metabolismo , Fármacos Anti-HIV/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Movimento Celular/imunologia , Microambiente Celular/imunologia , Técnicas de Cocultura , Células Dendríticas/imunologia , Células Dendríticas/virologia , Centro Germinativo/imunologia , Centro Germinativo/virologia , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Técnicas In Vitro , Linfonodos/imunologia , Linfonodos/virologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores Imunológicos/metabolismo , Receptores Virais/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/virologia , Transcrição Genética , Virulência
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