Immunophenotypic characteristics of Diffuse Large Bcell Lymphoma

Introduction: Immunohistochemistry (IHC) is essential in the diagnostic workup of Diffuse Large B cell lymphoma (DLBCL). Determination of biological heterogenicity of Diffuse Large B-cell Lymphoma (DLBCL) is critical to institute precise treatment and predict prognosis. IHC confirms B cell phenotypes, reflects molecular subtype based on cell of origin and determines other immunophenotypic characteristics. Methods and Material: All cases of DLBCL diagnosed in 2020 (Jan-Dec) in histopathology department of Evercare Hospital Dhaka were included in this study. Histopathological sections were stained with CD20, CD3, CD5, CD30, BCL2, BCL6, CD10, MUM1, MYC, Ki67 and other markers. Hans algorithm was applied to classify DLBCL cases into germinal center B-cell (GCB) or Non-GCB. Results: Out of 64 DLBCL cases, 21 (24%) of DLBCL were GCB, while 76% (43 cases) were non-GCB subtypes. 30% cases of DLBCL showed double expression for MYC and BCL2. Fewer cases were immunoreactive for CD5 and CD30. Conclusion: This first study at Dhaka with wide range of antibody to characterize the Immunophenotypic features of DLBCL. The main finding of this study is the identification of non-germinal center B-cell (non-GCB) as the major immunophenotype of DLBCL. This may be an enabler for further studies to observe the clinical outcome of different subtypes of GCB and Non-GCB. Bioresearch Commu. 8(1): 1049-1052, 2022 (January)

PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma

The synthesis of serine from glucose is a key metabolic pathway supporting cellular proliferation in healthy and malignant cells. Despite this, the role that this aspect of metabolism plays in germinal center biology and pathology is not known. Here, we performed a comprehensive characterization of the role of the serine synthesis pathway in germinal center B cells and lymphomas derived from these cells. We demonstrate that upregulation of a functional serine synthesis pathway is a metabolic hallmark of B-cell activation and the germinal center reaction. Inhibition of phosphoglycerate dehydrogenase (PHGDH), the first and rate limiting enzyme in this pathway, leads to defective germinal formation and impaired high-affinity antibody production. In addition, overexpression of enzymes involved in serine synthesis is a characteristic of germinal center B-cell derived lymphomas, with high levels of expression being predictive of reduced overall survival in diffuse large B cell lymphoma. Inhibition of PHGDH induces apoptosis in lymphoma cells reducing disease progression. These findings establish PHGDH as a critical player in humoral immunity and a clinically relevant target in lymphoma.

TREATMENT OUTCOMES AND CLINICAL RELEVANCE IN PATIENTS WITH DOUBLE EXPRESSOR DLBCL

Background: Double-expressor lymphoma (DEL) was found accounting for 20- 30% of DLBCL. We conducted this study to analyze the survival, the clinical presentation and the factors associated with treatment outcomes in DEL-DLBCL. Methods: A retrospective study of 291 patients diagnosed with DLBCL during January 2015 - December 2018. Results: Of the 291 patients, median age was 63 years, germinal center B cell like DLBCL (GCB) and non-GCB subtypes were found in 32% and 68%, respectively. DEL was found in 46% of 264 patients with available immunohistochemistry staining for MYC protein. Patients with DEL was significantly more common in elderly patients (p= 0.017) and non-GCB subtype (p= 0.006). High serum lactate dehydrogenase (LDH) levels and high Ki-67 index were significantly found in DEL patients than those in non-DEL patients (p= 0.024 and p= 0.04, respectively). 3y-OS and 3y-DFS in DEL patients were shorter than those in non-DEL group, 58.7% versus 78.9% (p=0.026) and 58.4% versus 67.7% (p=0.343), respectively. Independent factors affecting both OS and DFS in DEL patients were ECOG 3-4, high LDH level, extranodal involvement> 1 site, DHL, high IPI and stage III-IV. Conclusions: High incidence of DEL was observed in this study, especially in patients aged 60 years or older and non-GCB subtype. Patients with DEL showed dismal DFS and OS.

Emerging Landscape of Immunotherapy for Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is, mainly, a diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell (non-GCB) origin. It is associated with a poor prognosis and an unmet medical need. Immunotherapy has emerged as one of the most promising areas of research and is now part of the standard treatment for many solid and hematologic tumors. This new class of therapy generated great enthusiasm for the treatment of relapsed/refractory PCNSL. Here, we discuss the challenges of immunotherapy for PCNSL represented by the lymphoma cell itself and the specific immune brain microenvironment. We review the current clinical development from the anti-CD20 monoclonal antibody to CAR-T cells, as well as immune checkpoint inhibitors and targeted therapies with off-tumor effects on the brain microenvironment. Perspectives for improving the efficacy of immunotherapies and optimizing their therapeutic role in PCNSL are suggested.