Advances in understanding of angioimmunoblastic T-cell lymphoma

Chiba, Shigeru; Sakata‐Yanagimoto, Mamiko

doi:10.1038/s41375-020-0990-y

Cited by 118 publications

(132 citation statements)

References 121 publications

(298 reference statements)

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“…Interestingly, hypergammaglobulinemia was shown more in AITL, less in other TFH lymphomas [ 8 ]. In histopathologic findings, AITL is characterized by the proliferation of high endothelial venules and mixed inflammatory cell infiltration, which is not prominent in other TFH lymphomas [ 35 , 36 ]. Hypergammaglobulinemia is caused by increased immunoglobulin production of polyclonal plasma cells, and this phenomenon can be considered a result of specific immunogenic stimulation of AITL.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

et al. 2021

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Background The 2016 World Health Organization (WHO) classification introduced nodal lymphomas of T follicular helper (Tfh) cell origin, such as angioimmunoblastic T-cell lymphoma (AITL), follicular peripheral T-cell lymphoma (F-PTCL), and nodal peripheral T-cell lymphoma with T follicular helper phenotype (nodal PTCL with TFH phenotype). However, the accurate incidence rate and clinical characteristics of F-PTCL and nodal PTCL with TFH are unstudied. Methods Between February 2012 to June 2020, a total of 207 cases diagnosed with nodal lymphomas of T follicular helper (Tfh) cell origin and PTCL-NOS were reviewed for clinical and histopathologic data. PTCL-NOS was defined to not correlate to any of the specific entities of mature T cell lymphoma in the WHO 2016 classification. We attempted to classify PTCL-GATA3 and PTCL-TBX21 by IHC staining. Target gene analysis was performed on a few patients with sufficient blood and tissue samples additionally. Results Among 207 patients, 111 patients (53.6%) had AITL, 67 patients (32.4%) had PTCL-NOS, 19 patients (9.2%) had F-PTCL, and 10 patients (4.8%) had nodal PTCL with TFH phenotype. We re-defined and analyzed F-PTCL and nodal PTCL with TFH phenotype into other TFH lymphomas. AITL (N = 101/111, 91.0%) was found to have a higher frequency of stage III/IV cancers compared to other TFH lymphomas (N = 22/29, 75.0%) and PTCL-NOS (N = 53/67, 79.1%; p-value = 0.03). The OS of AITL and other TFH lymphomas was similarly superior to PTCL-NOS (p-value = 0.02). AITL and other TFH lymphomas showed the TBX21 subtype more commonly than the GATA3 subtype. Mutations related to the RAS family (RHOA) and those related to epigenetic regulators (IDH2, DNMT3A, and TET2) were shown mainly in AITL and other TFH lymphomas. Conclusions Other TFH lymphomas appear to be a rare disease entity around one-quarter in nodal lymphomas of T follicular helper (Tfh) cell origin. Their less aggressive clinical feature than we did not expect is utterly different from PTCL-NOS and AITL. On the other hand, other TFH lymphomas share some characteristics, such as the cell of origin, a more common TBX21 subtype, and genetic variation such as RAS family mutation and epigenetic regulators, with AITL.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

et al. 2021

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“…For example, in extranodal NK/T-cell lymphomas, the virus, detected in 71% of cases, infects tumor cells where it is constantly detected. Angioimmunoblastic T cell lymphoma (AITL), which is the focus of our work, is probably the most common form of PTCL [19] although less common in North America or Asia than in Europe, accounting respectively for 16-34.4%, 17.9-22.4%, and 28-34% of PTCLs [20,21]. AITL, which mostly affects elderly people [22], is clinically characterized by generalized lymphadenopathy often accompanied by hepatosplenomegaly, skin rash, and B-cell modifications associated with immunologic abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Epstein-Barr Virus Transcriptome by RNA-Sequencing in Angioimmunoblastic T Cell Lymphoma (AITL) and Other Lymphomas

Bayda

Tilloy

Chaunavel³

et al. 2021

Cancers

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The Epstein–Barr virus (EBV) is associated with angioimmunoblastic T cell lymphoma (AITL) in more than 80% of cases. Few studies have focused on this association and it is not clear now what role the virus plays in this pathology. We used next-generation sequencing (NGS) to study EBV transcriptome in 14 AITLs compared to 21 other lymphoma samples and 11 cell lines including 4 lymphoblastoid cell lines (LCLs). Viral transcripts were recovered using capture probes and sequencing was performed on Illumina. Bam-HI A rightward transcripts (BARTs) were the most latency transcripts expressed in AITLs, suggesting they may play a role in this pathology. Thus, BARTs, already described as highly expressed in carcinoma cells, are also very present in AITLs and other lymphomas. They were poorly expressed in cell lines other than LCLs. AITLs showed a latency IIc, with BNLF2a gene expression. For most AITLs, BCRF1, which encodes a homologous protein of human interleukin 10, vIL-10, was in addition expressed. This co-expression can contribute to immune escape and survival of infected cells. Considering these results, it can be assumed that EBV plays a pathogenic role in AITLs.

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“…10,16 Furthermore, immunohistochemical studies using four commercially available stains for GATA3, CXCR-4, T BX 21 and CXCR 3 in unformatted fixed paraffin embedded tissue can help classified the and the other type having depleted follicles. 21 The primary presentation of these two subtypes is nodal with a plethora of associated symptoms including arthralgias and skin rashes -autoimmune phenomena that can be explained by the role of T FH cells in the regulation of B cells. However, non-nodal presentations can occur especially in relapsed disease.…”

Section: Peripheral T-cell Lymphoma Not Other Specifiedmentioning

confidence: 99%

“…Downstream effects include inhibition of the TET2 family of Gene expression profiling of 114 cases of AITL has shown that potent angiogenic and pro inflammatory cytokines are expressed, including IL-8, IL6, IL18, IL-10 and IL21. The IDH2 mutations are also linked to increased blood vessel formation 21. This dysregulated function of the TFH induces a set of cytokines that result in the inflammatory components of AITL 23.…”

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confidence: 99%

Aggressive T‐cell lymphomas: 2021 Updates on diagnosis, risk stratification and management

Zain

Hanona²

2021

American J Hematol

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Introduction: Aggressive T-cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T-cell lymphoma (PTCL), and we are now beginning to understand the differences between the various subtypes beyond histologic variations. Molecular Pathogenesis of Various Subtypes of PTCL: Gene expression profiling (GEP) can help in diagnosis and prognostication of various subtypes including PTCLnos and anaplastic large cell lymphoma (ALCL). In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients. Targeted Therapies: There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. This includes the CD30 directed antibody drug conjugate brentuximab vedotin. Other notable targets are CD25, CCR4, inhibition of PI3kinasem TOR and JAK/STAT pathways. The ALK inhibitors are promising for ALK expressing tumors. Immunotherapies: Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL. The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T-cell (ENK/T) lymphomas and cutaneous T-cell lymphomas (CTCL). Bispecific antibody based treatments as well as CAR-T cell based therapies are in clinical trials.

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Advances in understanding of angioimmunoblastic T-cell lymphoma

Cited by 118 publications

References 121 publications

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

Comprehensive Epstein-Barr Virus Transcriptome by RNA-Sequencing in Angioimmunoblastic T Cell Lymphoma (AITL) and Other Lymphomas

Aggressive T‐cell lymphomas: 2021 Updates on diagnosis, risk stratification and management

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