PD-L1 and tumor-associated macrophages in de novo DLBCL
Ronald McCord, Christopher R Bolen, Hartmut Koeppen, Edward E Kadel 3rd, Mikkel Z Oestergaard, Tina Nielsen, Laurie H Sehn, Jeffrey M Venstrom, Ronald McCord, Christopher R Bolen, Hartmut Koeppen, Edward E Kadel 3rd, Mikkel Z Oestergaard, Tina Nielsen, Laurie H Sehn, Jeffrey M Venstrom
Abstract
Programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death-1 (PD-1), are important negative regulators of immune cell activation. Therapeutically targeting PD-1/PD-L1 in diffuse large B-cell lymphoma (DLBCL) patients with a single agent has limited activity, meriting a deeper understanding of this complex biology and of available PD-L1 clinical assays. In this study, we leveraged 2 large de novo DLBCL phase 3 trials (GOYA and MAIN) to better understand the biologic and clinical relevance of PD-L1 in de novo DLBCL. PD-L1 was expressed on myeloid cells in 85% to 95% of DLBCL patients (depending on staining procedure), compared with 10% on tumor cells, and correlated with macrophage gene expression. PD-L1 did not identify high-risk patients in de novo DLBCL; it correlated with STAT3, macrophage gene expression, and improved outcomes among a subset of patients. These results may help identify immunologically distinct DLBCL subsets relevant for checkpoint blockade. GOYA and MAIN trials were registered at www.clinicaltrials.gov as #NCT01287741 and #NCT00486759, respectively.
Conflict of interest statement
Conflict-of-interest disclosure: C.R.B., R.M., H.K., E.E.K., and J.M.V. are employed by Genentech and are shareholders in F. Hoffman-La Roche. M.Z.O. and T.N. are employed by, and are shareholders in, F. Hoffman-La Roche. L.H.S. declares no competing financial interests.
© 2019 by The American Society of Hematology.
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Source: PubMed