PD-L1 and PD-L2 Mutations in Pediatric Hodgkin Lymphoma: Do They Have Any Prognostic Significance?

Gül, Gülen; İnce, Dilek; Olgun, Nur; Özer, Erdener

doi:10.1080/15513815.2020.1764680

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…In a recently published our study, we sequenced exon and intron junction regions of the PD-L1 gene, and only 2 separate mutational variants were found in the exome 5 of the PD-L1 gene. Eight (20.5%) cases showed p.R260C mutation, and 3 (7.7%) cases showed additional p.R234L mutation 22. To evaluate the functional significance of this mutational change of the PD-L1 gene in our previous study, we compared PD-L1 mRNA levels of the mutated cases with negative tumors, but no significant difference was found.…”

Section: Discussionmentioning

confidence: 97%

“…Eight (20.5%) cases showed p.R260C mutation, and 3 (7.7%) cases showed additional p.R234L mutation. 22 To evaluate the functional significance of this mutational change of the PD-L1 gene in our previous study, we compared PD-L1 mRNA levels of the mutated cases with negative tumors, but no significant difference was found. Therefore, we speculate that this mutational change may have changed the amino acid sequence and structure of the protein and affect the PD-1/PD-L1 interaction instead of causing an overexpression.…”

Section: Discussionmentioning

confidence: 99%

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Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma

Gül

Ceyhan²,

İnce³

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Classic Hodgkin lymphoma (cHL) is one of the most common pediatric solid tumors and is responsible for cancer-related deaths in children. Therefore, to modulate the active antitumor T-cell immune response in cHL can be a treatment strategy. In the present study, we aimed to investigate the expression profiles of selected antitumor immune response genes in pediatric cHL and their relationships with clinical and prognostic parameters to determine their significance in precision medicine. Thirty-nine pediatric nodal cHL patients were enrolled in the study. We analyzed mRNA expression of selected immune response regulatory genes such as PD-L1, CSF2, CTLA4, CXCL5, IDO1, CXCL8, MIF, NOS2, PDCD1, PTGS2, and TGFβ1 using real-time quantitative polymerase chain reaction. Only PD-L1 overexpression was statistically related to bulky disease, advanced tumor stage, and high-risk disease category and seen significantly in Epstein-Barr virus-negative pediatric cHL. No expression profiles were correlated with relapse or survival. We conclude that PD-L1 overexpression in pediatric cHL cases is a strong predictor of highrisk categorization. In addition to being a prognostic biomarker, PD-L1 blockade is also a druggable marker for the targeted therapy in Epstein-Barr virus-negative pediatric Hodgkin lymphoma.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma

Gül

Ceyhan²,

İnce³

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

Self Cite

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“…Sanger sequence method was used in one study on 40 paediatric CHL patients. Of the patients, 20.5% had p.R260C and 7.7% had p.R234L mutations on exon 5 of PD-L1 locus [ 34 ]. In a small-scale next generation sequencing (NGS) study performed on 4 CHL patients who were positive for PD-L1 with immunohistochemistry, despite 3 of the patients were PD-L1 amplified by FISH, none were amplified by NGS method [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Gül et al found significant correlation between pR260c mutation on exon 5 of PD-L1 gene and nodular sclerosing subtype and event-free survival in older paediatric patients. This may be due to decreased functionality in the mutant protein [ 34 ]. In our study, clinical data of 39 patients were examined, no significant relationship was found between PD-L1 positivity and age, sex, histological subtype of CHL, clinical stage, presence of spleen, bone marrow, or other extranodal organ involvement at the time of diagnosis.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 and EBV LMP1 expressions in classic Hodgkin lymphomas and its correlation with clinicopathological parameters and prognosis

ÖZDEMİR¹,

TON²,

KABUKCUOĞLU³

2022

Turkish Journal of Medical Sciences

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Background/aim Programmed death pathway leads to T cell anergy. Wide range of malignancies take advantage of this pathway by programmed death-ligand 1 (PD-L1) expression either on neoplastic cells or on the nonneoplastic cells of tumour microenvironment. New therapeutic approaches have been directed against this pathway. We studied PD-L1 expression on both neoplastic Hodgkin and Reed–Sternberg (HRS) cells and cells of tumour microenvironment in classic Hodgkin lymphoma (CHL) patients and compared it with Ebstein–Barr virus (EBV) positivity, clinical data, and survival rates. Materials and methods Lymph node excision materials of 56 CHL patients diagnosed between 2007 and 2017 were included in this retrospective study. PD-L1 expression of HRS cells and tumour microenvironment cells were evaluated by immunohistochemical assay. Staining intensity and rate of the PD-L1 expressions were estimated. EBV was examined by immunohistochemistry for latent membrane protein 1 (LMP1) antibody. Clinical data of 39 patients and survival data of 34 patients were compared with PD-L1 expressions on tumour cells. Results PD-L1 expression was present in HRS cells in 89.2% of the cases. There was more than 20% of PD-L1 expression in cells of tumour microenvironment in all the cases. PD-L1 positivity did not show statistically significant difference according to EBV expression, clinical parameters, and prognosis. Conclusion Previous studies showed inconsistent rates for PD-L1 prevalence (20%–95.7%) in CHL patients due to differences in the study methods. Although high prevalence of PD-L1 positivity was found in majority of them, there was no statistically significant difference between PD-L1 positivity on HRS cells and EBV expression, clinical parameters, and prognosis. This high prevalence in patients with various clinical properties makes PD-L1 a potential target for new emerging immunotherapies for CHL.

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Combination Therapy With Anti-PD-1 or PD-1 Antibody Alone in Asian Pediatric Patients With Relapsed or Refractory Cancer

et al. 2021

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There is limited experience of PD-1 antibody combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. This is a retrospective-case study conducted in two Chinese expert centers. The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities. Of the 22 pediatric patients with cancer who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0 - 43 months). PD-1 antibody monotherapy demonstrated antitumor activity in a population of pediatric patients with Hodgkin lymphoma (HL), with an objective response rate (ORR) and disease control rate (DCR) of 83.3% (3CR and 2PR) and 100%, respectively. However, no objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. We reviewed responses for patients with chemotherapy, decitabine or everolimus combination therapies with PD-1 antibodies, and found that PD-1 antibody combined with decitabine showed potential efficacy in pediatric patients with advanced embryonal rhabdomyosarcoma and lymphoepitheliomatoid-like carcinoma. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 antibody monotherapy in Asian pediatric patients with lower incidence of hematologic toxicity and nonhematologic toxicity. The Grade ≥3 TRAEs were attributed to the combination chemotherapy.

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PD-L1 and PD-L2 Mutations in Pediatric Hodgkin Lymphoma: Do They Have Any Prognostic Significance?

Cited by 3 publications

References 23 publications

Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma

Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma

PD-L1 and EBV LMP1 expressions in classic Hodgkin lymphomas and its correlation with clinicopathological parameters and prognosis

Combination Therapy With Anti-PD-1 or PD-1 Antibody Alone in Asian Pediatric Patients With Relapsed or Refractory Cancer

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