Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

Duffield, Amy S.; Ascierto, Maria Libera; Anders, Robert A.; Taube, Janis M.; Meeker, Alan K.; Chen, Shuming; McMiller, Tracee L.; Phillips, Neil A.; Xu, Huimin; Ogurtsova, Aleksandra; Berger, Alan E.; Pardoll, Drew M.; Topalian, Suzanne L.; Ambinder, Richard F.

doi:10.1182/bloodadvances.2017007260

Cited by 38 publications

(42 citation statements)

References 48 publications

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“…Duffield et al. recently found increased infiltration of CD8 + T cells in EBV‐positive classical HL samples, which we noted in the patients with MC subtype, all of which were EBV positive . We did not note a significant difference, however, when comparing EBV‐positive and EBV‐negative NS cases.…”

Section: Discussioncontrasting

confidence: 59%

“…We also found a correlation between CD4/CD8 ratio and WBC, indicating a possible link between WBC and tumor biology, although many factors may influence WBC in this setting. 26 We did not note a significant difference, however, when comparing EBV-positive and EBV-negative NS cases.…”

Section: Discussionmentioning

confidence: 55%

“…The significantly high incidence of EBV positivity in MC cases and the intermediate CD4/CD8 ratio seen in EBV positive NS cases suggest that EBV is involved in shaping the microenvironment in children with HL, expanding on the existing literature . Duffield et al.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies have found patterns in the immunohistochemical profile that may be specific to HL. The immunophenotype of EBV‐positive tumors has also been shown to be modulated by the virus . However, no single immunophenotype has been associated with either histologic subtypes or prognosis of HL.…”

Section: Introductionmentioning

confidence: 99%

“…The immunophenotype of EBV-positive tumors has also been shown to be modulated by the virus. 12,24,26 However, no single immunophenotype has been associated with either histologic subtypes or prognosis of HL. Understanding the relationship between the microenvironment and the behavior of HL may allow us to identify biomarkers for disease.…”

Section: Introductionmentioning

confidence: 99%

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Flow cytometry for assessment of the tumor microenvironment in pediatric Hodgkin lymphoma

Henry

Buck

Savaşan

2018

Pediatric Blood & Cancer

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Flow cytometry for assessment of the tumor microenvironment in pediatric Hodgkin lymphoma

Henry

Buck

Savaşan

2018

Pediatric Blood & Cancer

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The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profile, EBV, and exosomes

2020

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Background: Classical Hodgkin lymphoma (cHL) is a unique lymphoid malignancy with a tumor microenvironment (TME) consisting of a small number of neoplastic—Hodgkin and Reed‐Sternberg (H‐RS) cells (<1%), surrounded by a large number of nonneoplastic infiltrating immune cells (>90%). The TME of cHL critically depends on immune cells to support tumor growth as H‐RS cells cannot survive and proliferate in isolation. Recent Findings: Programmed cell death protein 1 (PD‐1) ligand expressed on H‐RS cells inhibits the clearance of tumor by causing T‐cell exhaustion. Nivolumab and pembrolizumab, PD‐1 inhibitors, have been proven to be effective in treating adult and pediatric patients with R/R cHL. Tumor‐associated macrophages (TAMs) are a central component of TME and are known to cause poor prognosis in adult HL. However, the prognostic impact of CD68+ TAMs in pediatric HL remains ambiguous. EBV modulates the tumor milieu of HL and plays a strategic role in immune escape by enrichment of the TME with Treg cells and associated immunosuppressive cytokines in adult HL. In contrast, EBV+ pediatric patients have increased infiltration of CD8+ T‐cells and show a better therapeutic response suggesting viral‐related TME is distinct in childhood HL. The role of CASP3 in apoptosis of H‐RS cells and its correlation with response prediction in adult and pediatric HL suggest it may serve as a potential biomarker. In cHL, CD30, EBV, and NF‐κB signaling employ exosomes for cell–cell communication that triggers the migration capacity of fibroblasts, stimulate to produce proinflammatory cytokines, and help to create a tumor‐supportive microenvironment. Conclusion: The cHL microenvironment is distinct in adult and pediatric HL. Future studies are required to understand the role of interplay between H‐RS cells and EBV‐associated microenvironment and their clinical outcome. They may present novel therapeutic targets for the development of antilymphoma therapy.

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Flow cytometric analysis of fine needle aspirates is affected by tumor subtype, but not by anatomic location nor technique

Wake

VandenBussche

Ali

et al. 2020

Diagnostic Cytopathology

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BackgroundCurrent clinical practices are shifting towards utilizing less invasive biopsy techniques, including fine needle aspiration (FNA) and needle core biopsies. If a patient has a suspected hematologic malignancy, a portion of the FNA sample is typically submitted for flow cytometry (FC) analysis, providing valuable immunophenotypic data.MethodsFNA specimens were identified via a pathology database search. All cases were morphologic evaluated and a subset of cases were analyzed by FC.Results245 hematologic FNA specimens were identified; 84% of these cases had an adequate number of cells for FC analysis, and an unequivocal morphologic diagnosis (benign or malignant) was rendered in 85%. The percentage of cases with an unequivocal diagnosis was statistically significantly higher in those with associated FC than with those without FC (90% vs 58%). Neither FNA technique nor anatomic site affected the likelihood of obtaining an adequate sample for FC analysis and/or rendering a definitive morphologic or unequivocal FC diagnosis. Likewise, tumor subtype did not affect the likelihood of acquiring enough cells for FC analysis, but occasionally resulted in equivocal FC diagnoses or discordant FNA and FC diagnoses. Aggressive B‐cell lymphomas and Hodgkin lymphomas were significantly less likely to be detected by FC as compared to low‐grade B‐cell lymphomas. Discrepancies between FNA and FC diagnoses occurred in 13% of cases. The majority of discrepancies (78%) included FC false negatives, while only 22% of cases had atypical or positive FC with negative FNA.ConclusionsFNA with associated FC is a powerful diagnostic technique; however, lymphoma subtype may affect diagnostic sensitivity by FC, and therefore, discordant FNA and FC results should be interpreted with caution.

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Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

Cited by 38 publications

References 48 publications

Flow cytometry for assessment of the tumor microenvironment in pediatric Hodgkin lymphoma

Flow cytometry for assessment of the tumor microenvironment in pediatric Hodgkin lymphoma

The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profile, EBV, and exosomes

Flow cytometric analysis of fine needle aspirates is affected by tumor subtype, but not by anatomic location nor technique

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