PD-L1 and tumor-associated macrophages in de novo DLBCL

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.

PD‐L1 expression is low in large B‐cell lymphoma with MYC or double‐hit translocation

“…12 In contrast, others found that PD-L1 was expressed in some DLBCL tumour cells. [8][9][10][11] Our results support the latter findings.…”

“…In line with this, overexpression of PD‐L1 in tumour cells has been identified as an independent adverse prognostic marker associated with inferior outcome in several studies including studies of DLBCL . However, one study suggests an association of PD‐L1 and better prognosis in some de novo DLBCL patients …”

“…We investigated the relationship between PD‐L1 expression and MYC and DH translocation and found a negative association between PD‐L1 expression levels in tumour cells and the presence of MYC and DH translocation in patients with LBCL. We aimed at investigating this relationship in order to achieve more consistent results as studies on PD‐L1 expression in LBCL up until now are few and show inconsistent results . Treatments targeting the PD‐L1/PD‐1 pathway has been successfully introduced in treatment of Hodgkin lymphoma and some solid cancers, but results are sparse regarding the effect of treatment in LBCL, and as PD‐L1 expression in tumour cells seems to predict outcome to treatment in Hodgkin lymphoma, it may do the same in LBCL.…”

“…We aimed at investigating this relationship in order to achieve more consistent results as studies on PD-L1 expression in LBCL up until now are few and show inconsistent results. [8][9][10][11][12] Treatments targeting the PD-L1/PD-1 pathway has been successfully introduced in treatment of Hodgkin lymphoma and some solid cancers, 4,5,7 but results are sparse regarding the effect of treatment in LBCL, and as PD-L1 expression in tumour cells seems to predict outcome to treatment in Hodgkin lymphoma, 7 it may do the same in LBCL.…”

“…6,7 However, one study suggests an association of PD-L1 and better prognosis in some de novo DLBCL patients. 8 PD-L1 expression in DLBCL has been investigated in a few studies. [9][10][11][12] Expression of PD-L1 in tumour cells seems to predict response to therapy with PD-L1/PD-1 inhibitors in Hodgkin lymphoma, 7 and further studies will elucidate whether it can be used as a predictive marker in DLBCL as well.…”