Hodgkin Lymphoma: Biology and Differential Diagnostic Problem

Takahara, Taishi; Satou, Akira; Tsuzuki, Toyonori; Nakamura, Shigeo

doi:10.3390/diagnostics12061507

Cited by 4 publications

(5 citation statements)

References 159 publications

(182 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TOX and TOX2 [11]. A high percentage (>75%) of tumor-infiltrating CD4 + T cells was associated with decreased freedom from treatment failure (FFTF) [12].…”

Section: Cd4 + T-cellsmentioning

confidence: 99%

“…The most abundant cellular population in the TME of HL comprises CD4 + T cells, with a T-helper (T h ) phenotype, which tend to gather around HRS cells in formations called rosettes ( Figure 1 ). These cells express T cell exhaustion markers including PD-1, TOX and TOX2 [ 11 ]. A high percentage (>75%) of tumor-infiltrating CD4 + T cells was associated with decreased freedom from treatment failure (FFTF) [ 12 ].…”

Section: Overview Of Cellular Components Of Tme In Chlmentioning

confidence: 99%

“…These ligands bind to PD-1 receptors on T cells, which inhibits their activation and proliferation, leading to T cell exhaustion. Interestingly, in cHL, PD-L1 is also expressed by TAMs which co-localize with HRS cells, thus augmenting the immunosuppressive signals against host immunity [ 11 , 63 , 99 ]. HRS cells have been shown to be capable of transferring PD-L1 molecules to TAMs’ surface via trogocytosis, a process that enables neighboring cells to exchange membrane molecules, which underlines the role of HRS cells in actively shaping their microenvironment to their benefit [ 100 ].…”

Section: Immune Evasionmentioning

confidence: 99%

See 2 more Smart Citations

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

Georgoulis

Papoudou‐Bai

Makis

et al. 2023

Biology

View full text Add to dashboard Cite

Classic Hodgkin lymphoma (cHL) is a lymphoid neoplasm composed of rare neoplastic Hodgkin and Reed–Sternberg (HRS) cells surrounded by a reactive tumor microenvironment (TME) with suppressive properties against anti-tumor immunity. TME is mainly composed of T cells (CD4 helper, CD8 cytotoxic and regulatory) and tumor-associated macrophages (TAMs), but the impact of these cells on the natural course of the disease is not absolutely understood. TME contributes to the immune evasion of neoplastic HRS cells through the production of various cytokines and/or the aberrant expression of immune checkpoint molecules in ways that have not been fully understood yet. Herein, we present a comprehensive review of findings regarding the cellular components and the molecular features of the immune TME in cHL, its correlation with treatment response and prognosis, as well as the potential targeting of the TME with novel therapies. Among all cells, macrophages appear to be a most appealing target for immunomodulatory therapies, based on their functional plasticity and antitumor potency.

show abstract

“…TOX and TOX2 [11]. A high percentage (>75%) of tumor-infiltrating CD4 + T cells was associated with decreased freedom from treatment failure (FFTF) [12].…”

Section: Cd4 + T-cellsmentioning

confidence: 99%

Section: Overview Of Cellular Components Of Tme In Chlmentioning

confidence: 99%

Section: Immune Evasionmentioning

confidence: 99%

See 1 more Smart Citation

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

Georgoulis

Papoudou‐Bai

Makis

et al. 2023

Biology

View full text Add to dashboard Cite

show abstract

“…We analysed the clinical features of patients with lymph node-reactive hyperplasia or Hodgkin's lymphoma and found no differences between the two groups. Therefore, we raised questions about why people in the same area and same living environment with the same population attributes would have different disease outcomes after infection with Epstein-Barr virus [9,10].We suspected that this difference in outcome was the result of an interaction between the body's own immune system and external antigenic stimulation, which would be related to differences in the antigens recognized by he immune cells on the one hand and the microenvironment of the tumour cells on the other hand.…”

Section: Discussionmentioning

confidence: 99%

Study on the inflammatory microenvironment of Epstein‒Barr virus-infected Hodgkin's lymphoma

Li,

2024

Preprint

View full text Add to dashboard Cite

Background Epstein-Barr virus (EBV) is common in patients with Hodgkin's lymphoma (HL). It can lead to a loss of immune function, greatly increasing the HL risk. Clinical characteristics of RLH (reactive lymphoid hyperplasia) group and HL group were analyzed, and differences in cell morphology and CD30 expression were detected. Results There were no differences in clinical features between the RLH and HL groups. In terms of immune cell activity, compared with the RLH group, the HL group exhibited decreased proportions of CD4 + T cells and NK cells in lymphocytes, while the proportions of CD8 + T cells and CD19 cells were increased. The average expression rate of PD-1 was 51.14%, which indicated high expression. The expression of immune response products were significantly increased, and the expression of RIP2 was significantly decreased. The expression rates of IL-1β, IFN-α, INF-γ, TNF-α, IL-10, IL-6, IL-18, IL-17A, IL-8, IL-12P70, MCP-1, IL-23 and IL-33 were all increased in the patient group. WP5095, hsa04061, R-HSA-6785807, M196, hsa05321, and GO: 0032675 were significantly enriched pathways. Conclusions The changes of immune factors and inflammatory factors may also provide ideas for continuing to explore the biological treatment of EB positive Hodgkin lymphoma.

show abstract

“…Pathologically, they consist of large tumor cells, known as HRS cells, in a reactive inflammatory background. Recent studies have revealed that immune evasion plays a key role in the development of CHLs 6,7 . Among the multiple factors related to the immune evasion of HRS cells, the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway is regarded as particularly important 8 .…”

mentioning

confidence: 99%

Diagnostic Utility of STAT6 and pSTAT6 Immunohistochemistry for Distinguishing Classic Hodgkin Lymphoma and Peripheral T-Cell Lymphoma With Hodgkin and Reed-Sternberg–like Cells

Satou

Takahara

Yamashita

et al. 2023

American Journal of Surgical Pathology

Self Cite

View full text Add to dashboard Cite

Peripheral T-cell lymphomas (PTCLs), particularly nodal lymphomas of T-follicular helper cell origin, may include Hodgkin/Reed-Sternberg (HRS)-like cells in their microenvironment. These HRS-like cells are morphologically indistinguishable from HRS cells of classic Hodgkin lymphoma (CHL). Therefore, PTCLs with HRS-like cells pose a differential diagnosis vis-à-vis CHL. A previous study reported that, in contrast to HRS cells, programmed death-ligand 1 (PD-L1) expression is rare in HRS-like cells of PTCLs and suggested that PD-L1 immunohistochemistry is useful to differentiate HRS cells and HRS-like cells. In this study, we analyzed 21 patients with PTCL with HRS-like cells and 34 patients with CHL and assessed the diagnostic utility of STAT6, pSTAT6, and pSTAT3 immunohistochemistry in distinguishing HRS cells from HRS-like cells. In addition, we also performed PD-L1 immunohistochemistry to reconfirm its utility in distinguishing the 2 diseases. Compared with HRS cells in CHLs, HRS-like cells in PTCLs showed significantly less positivity for STAT6 (9.6% vs. 70%, P<0.001), pSTAT6 (9.6% vs. 70%, P<0.001), and PD-L1 (9.6% vs. 85%, P<0.001). Thus, we reconfirmed the diagnostic utility of PD-L1 immunohistochemistry in distinguishing CHLs from PTCLs with HRS-like cells. In contrast, both HRS-like and HRS cells were highly associated with pSTAT3 expression, with no significant difference in positive cell frequency (86% vs. 91%, P=0.66). On the basis of these findings, we conclude that, in addition to PD-L1, STAT6 and pSTAT6 immunohistochemistry are helpful diagnostic tools to distinguish CHLs from PTCLs with HRS-like cells.

show abstract

Hodgkin Lymphoma: Biology and Differential Diagnostic Problem

Cited by 4 publications

References 159 publications

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

Unraveling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

Study on the inflammatory microenvironment of Epstein‒Barr virus-infected Hodgkin's lymphoma

Diagnostic Utility of STAT6 and pSTAT6 Immunohistochemistry for Distinguishing Classic Hodgkin Lymphoma and Peripheral T-Cell Lymphoma With Hodgkin and Reed-Sternberg–like Cells

Contact Info

Product

Resources

About