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Abstract: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type non-Hodgkin’s lymphoma, where the treatment of relapsed/refractory cases is the major challenge. Programmed cell death protein 1 (PD-1) and its ligand PD-L1 play a crucial role in the negative regulation of the immune response against the disease. The aim of the study was to analyze the expression of PD-1 and PD-L1 on lymphoma cells (LCs) and tumor-immune cells (TICs) and to investigate their correlation with outcome. Samples from 283 patients diagnosed with DLBCL, NOS (both germinal center B cell like [GCB] and non-GCB subtypes) were included in the study. Expression of PD-1 and PD-L1 was determined using double immunohistochemical staining (D-IHC) for PD-1/PAX5 and PD-L1/PAX5 on tissue microarrays. LCs were highlighted by D-IHC to obtain more accurate results. Clinical data and histologic diagnoses were obtained from electronic data records. We correlated clinical characteristics, and PD-1 and PD-L1 expression on LCs and TICs with progression-free survival (PFS) and overall survival (OS). Expression of PD-1 on TICs was observed in 38.4% and on LCs in 8.8% of cases, while PD-L1 was expressed on TICs in 46.8% and on LCs in 6.5% of cases. PD-L1 expression on LCs was more frequent in non-GCB subtype (p = 0.047). In addition, patients with PD-L1 expression on LCs had significantly shorter PFS (p = 0.015), and the expression retained significant in the multivariate model (p = 0.034). PD-L1 was more frequently expressed in LCs of the non-GCB subtype. Additionally, PD-L1 in LCs may predict shorter PFS time. D-IHC staining for PD-L1/PAX5 is a feasible method to assess PD-L1 expression on LCs of DLBCL, NOS patients and can be used to identify patients who may benefit from targeted immunotherapy with checkpoint inhibitors.
Keywords: diffuse large b-cell lymphoma, immunohistochemistry, cytopathology
Published in DiRROS: 26.06.2026; Views: 220; Downloads: 96
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Abstract: Adjuvant nivolumab has become the new standard of care for patients with oesophageal and gastroesophageal junction cancer (OEC/GEJC) following neoadjuvant chemoradiotherapy (neoCRT) and surgical resection. In Slovenia, this treatment has been in use since January 2022. Here, we report the first Slovenian real-world experience with adjuvant nivolumab. Patients and methods. We conducted a retrospective, observational cohort study of patients with OEC/GEJC who received adjuvant nivolumab after neoCRT and radical resection between January 2022 and December 2023. Data on patient characteristics, treatment completion, disease progression, and immune-related adverse events (irAEs) were collected from medical records and analysed via descriptive statistics. Results. A total of 17 patients were included. The median follow-up was 34.6 months (range 11.2–55.7). The cohort included 14 (82%) males, with a mean age of 59 years. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 15 (88%) patients and 1 for 2 (12%) patients. The tumor location was the esophagus in 9 (53%) patients and the gastroesophageal junction in 8 (47%) patients. At diagnosis, 13 (76%) patients were stage III (8th TNM classification). Histology revealed adenocarcinoma (AC) in 12 (71%) patients and squamous cell carcinoma (SCC) in 5 (29%) patients. Only 6 (35%) patients completed one year of adjuvant nivolumab. Treatment was discontinued in 5 (29%) patients due to disease progression and in 6 (35%) patients due to irAEs. Overall, 11 (65%) patients experienced irAEs of any grade. Grade 3 or 4 irAEs occurred in 4 (24%) patients: myocarditis G4 in 1 (6%) patient and colitis G3 in 3 (18%) patients. No irAE-related deaths were reported. The median disease-free survival (DFS) was 21.4 months (95% confidence interval [CI], 14.6–28.9). Conclusions. Real-world data from Slovenia indicate that 65% of patients discontinued adjuvant nivolumab prematurely due to disease progression or irAEs. These findings highlight the need for careful patient selection and monitoring when using adjuvant immunotherapy in this population.
Keywords: oesophageal cancer, gastroesophageal junction cancer, adjuvant immunotherapy, nivolumab
Published in DiRROS: 18.06.2026; Views: 216; Downloads: 89
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Published in DiRROS: 25.02.2026; Views: 516; Downloads: 153
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Keywords: limfomi, patologija, onkologija
Published in DiRROS: 25.02.2026; Views: 488; Downloads: 134
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Abstract: Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes. This study aimed to evaluate the effectiveness of the Archer FusionPlex Lymphoma Assay in identifying the newly defined genetic subtypes of DLBCL, while also exploring the association between immunohistochemical (IHC) and next-generation sequencing (NGS) methods for classifying the cell of origin (COO) and assessing their predictive value for patient survival. Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-celllike) and ABC (activated B-cell-like) subtypes, and with NGS applying Archer FusionPlex lymphoma assay into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes. Finally, STRATOS analysis was conducted to validate our preliminary statistical findings. Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between IHC and NGS method for COO determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. The inclusion of these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only. Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth STRATOS statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.
Keywords: diffuse large B-cell lymphoma, new genetic types, prognostic factors
Published in DiRROS: 26.11.2025; Views: 759; Downloads: 214
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