Patterns of immune checkpoint protein expression in MYC-overexpressing aggressive B-cell non-Hodgkin lymphomas
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RESEARCH REPORT
Patterns of immune checkpoint protein expression in MYC‑overexpressing aggressive B‑cell non‑Hodgkin lymphomas Daniel J. Landsburg1 · Alexa Koike1 · Sunita D. Nasta1 · Jakub Svoboda1 · Stephen J. Schuster1 · Mariusz A. Wasik2 · Gabriel C. Caponetti1 Received: 4 July 2020 / Accepted: 19 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Given the poor prognosis of MYC-overexpressing diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma/high grade B cell lymphoma (BCLU/HGBL), and preclinical data suggesting that MYC may regulate the antitumor immune response, we sought to characterize expression of immune checkpoint proteins on tumor tissue from patients diagnosed with these lymphomas. Immunohistochemical staining for immune checkpoint protein expression was applied to 56 cases of MYC-overexpressing DLBCL and BCLU/HGBL, 35 of which also harbored MYC rearrangement (MYC-R). Analysis revealed both frequent overexpression of immune checkpoint proteins as well as differences in overexpression patterns based upon MYC-R status, with MYC-R cases more likely to overexpress PD-L1 and PD-1 in the tumor microenvironment (50 vs. 15%, p = 0.02 and 32 vs. 5%, p = 0.02, respectively) but less likely to overexpress CTLA-4 and CD80 on tumor cells (34 vs. 71%, p = 0.01 and 34 vs. 81%, p = 0.001, respectively), as compared to cases without MYC-R. These data may suggest a biologic rationale for investigation of the effect of checkpoint inhibitor therapies in these subgroups of MYC-overexpressing DLBCL and BCLU/HGBL. Keywords MYC · Diffuse large B cell lymphoma · High grade B cell lymphoma · PD-1 · PD-L1
Introduction Patients diagnosed with diffuse large B cell lymphoma (DLBCL) and the recently re-classified histology of B cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma/high grade B cell lymphoma (BCLU/HGBL) experience variable outcomes following receipt of the standard front-line immunochemotherapy regimen of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). One of the more wellcharacterized poor prognosis features of these diseases at initial diagnosis is the presence of MYC rearrangement (MYC-R) [1, 2] as well as overexpression of MYC protein [3, 4], independent of MYC-R status, and testing for these MYC alterations is frequently performed in clinical practice.
* Daniel J. Landsburg [email protected] 1
University of Pennsylvania, Philadelphia, PA, USA
Fox Chase Cancer Center and University of Pennsylvania, Philadelphia, USA
2
Given a high likelihood that patients with these MYC-altered lymphomas will develop chemorefractory disease, treatment with non-cytotoxic agents may be beneficial. Immune checkpoint inhibitors have emerged as effective therapies in solid tumor malignancies as well as classical Hodgkin lymphoma, and has led to approval of inhibitors of programmed cell death protein 1 (PD-1), p
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