Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression.
This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018.
Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL.
The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.
KeywordsDLBCL PD-L1 Gastric lymphoma Intestinal lymphoma Gastrointestinal lymphoma
Died of disease
Diffuse large B-cell lymphoma
Died of other causes
Epstein-Barr virus-encoded small RNA
Gastric diffuse large B-cell lymphoma
Gastric and intestinal diffuse large B-cell lymphoma
Intestinal diffuse large B-cell lymphoma
Programmed cell death ligand 1 expression on microenvironment immune cells
No evidence of disease
Recurrence of disease at 24 months or later
Programmed cell death ligand 1 expression on neoplastic cells
Programmed cell death ligand 1
- R-containing chemotherapy
Recurrence of disease within 24 months
The authors thank Y. Katayama, Y. Inagaki, K. Matsubara, and K. Kito for technical assistance and the following collaborators for providing patient clinical data and specimens: Aichi Cancer Center Hospital, Anjo Kosei Hospital, Ekisaikai Hospital, Fujita Health University, Ishikawa Prefectural Central Hospital, Japanese Red Cross Nagoya Daini Hospital, Kani Tono Hospital, Kariya Toyota General Hospital, Koseiren Takaoka Hospital, Matsue City Hospital, Ogaki Municipal Hospital, Okazaki Municipal Hospital, Omihachiman Community Medical Center, Shizuoka Saiseikai General Hospital, Suzuka Chuo General Hospital, Takatsuki General Hospital, Toyota Kosei Hospital, Toyota Memorial Hospital, Toyama Prefectural Central Hospital, Toyohashi Medical center, and Toyohashi Municipal Hospital.
EI, SN, and MF: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, revision of the manuscript, statistical analysis. SK, KS, AS, and KK: acquisition of data, analysis and interpretation of data. Rest of authors: acquisition of data. All authors approved the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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