Background: Antitumor immune response of programmed cell death ligand (PD-L1) has shown clinical value not only in Hodgkin lymphoma and EBV-associated lymphomas but also in EBV-negative diffuse large B cell lymphoma (DLBCL) of non-germinal center B cell-like (non-GCB) subtype. Signal transducer and activator of transcription 3 (STAT3) is known to induce PD-L1 in immune cells and its activated form, phosphorylated STAT3 (pSTAT3), is also frequently expressed in non-GCB DLBCL. Herein, we investigated associations between PD-L1 expression/gene alteration, pSTAT3 expression and clinicopathologic variables in EBV-negative DLBCL.
Methods: In 107 cases of DLBCLs with non-GCB subtype (67%; 72/107), GCB subtype (25%; 27/107) and unclassifiable cases (8%; 8/107), we performed PD-L1 and pSTAT3 immunohistochemistry and fluorescence in situ hybridization for PD-L1 gene translocation and copy number gain/amplification.
Results: PD-L1 was expressed in tumor cells (PD-L1t) in 21% (23/107; 30% cutoff), immune cells (PD-L1i) in 36% (38/107; 20% cutoff), and pSTAT3 in tumor nuclei in 41% (44/107; 40% cutoff). PD-L1 gene alteration was observed in 10% (10/102) including translocation in 6% (6/102) and copy number gain/amplification in 4% (4/102). Non-GCB subtype was associated with PD-L1t and pSTAT3 (p = 0.006 and p = 0.042), and tended to have PD-L1 gene alteration (p = 0.058). Tumoral PD-L1 expression without gene alteration (PD-L1t+ GA-) correlated with pSTAT3-positive tumor cell proportions (%) (p = 0.033). In survival analysis, pSTAT3 expression independently predicted shorter PFS in total cohort (p = 0.017) and R-CHOP-treated group (p = 0.007), and in pSTAT3-negative R-CHOP-treated subset, PD-L1 expression in immune cells (PD-L1i) correlated with shorter PFS (p = 0.042).
Conclusions: Gene alteration and protein expression of PD-L1 and pSTAT3 expression were closely related in DLBCL and constituted features of non-GCB subtype. In addition to known clinical significance of pSTAT3, immune cell expression of PD-L1 (PD-L1i) had also clinical value in pSTAT3-dependent manner. These findings may provide an insight into immunotherapeutic strategy and risk stratification in DLBCL patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245852 | PMC |
| http://dx.doi.org/10.1186/s12967-018-1689-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B-Cell Lymphoma: A Real-World, Multi-Center, Retrospective Cohort Study.
Hematol Oncol
January 2025
Department of Lymphoma, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China.
View Article and Find Full Text PDFExpression of MYD88 L265P Mutation in Subtypes of Diffuse Large B-Cell Lymphoma in the Pakistani Population.
Appl Immunohistochem Mol Morphol
January 2025
Department of Histopathology.
Article Synopsis
- The MYD88 L265P mutation, linked to increased cancer cell activity, is prevalent in Waldenstrom macroglobulinemia and non-germinal center diffuse large B-cell lymphoma (DLBCL) but its occurrence in the Pakistani population is not well-documented.
- A study at the Armed Forces Institute of Pathology analyzed 82 DLBCL cases, finding the mutation in 3.6% of germinal center B-cell (GCB) subtype and 22.2% of non-GCB subtype cases.
- The significant association (P = 0.024) suggests that targeting this mutation could improve treatment outcomes for DLBCL patients, especially those with the non-GCB subtype.
Real-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.
Ann Hematol
December 2024
Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore, 168583, Singapore.
Background: Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity.
Methods: We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens.
High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma : Identification of an MCD-like Subtype.
Am J Surg Pathol
February 2025
Departments of Pathology and Oncology.
Article Synopsis
- Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare and aggressive type of lymphoma, predominantly associated with genetic mutations MYD88 L265P and CD79B Y196, which indicate a poor prognosis.
- In a study involving 55 patients, researchers utilized droplet digital PCR and FISH to identify these mutations and translocations, finding high prevalence rates (52.7% for MYD88 and 36.4% for CD79B), with 58.2% of cases categorized as the aggressive MCD-like subtype.
- The MCD-like subtype showed a tendency for relapse in areas like the CNS and had worse overall and progression-free survival rates compared to the co-wild type
Clinicopathological and genetic analyses of thyroid large B-cell lymphoma in a Japanese population.
J Clin Exp Hematop
December 2024
Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan.
Article Synopsis
- Primary thyroid lymphoma, a rare cancer primarily consisting of large B-cell lymphomas (LBCLs), has a favorable prognosis and its underlying reasons are being studied.
- Analysis of 21 cases revealed that most patients (71%) had limited-stage disease and a 5-year overall survival rate of 83%, with no central nervous system recurrences observed.
- Factors linked to better clinical outcomes included a higher percentage of germinal center B-cell (GCB) phenotypes and an absence of MYD88 mutations among the cases.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!