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J Transl Med. 2018 Nov 20;16(1):320. doi: 10.1186/s12967-018-1689-y.

Clinicopathologic implication of PD-L1 and phosphorylated STAT3 expression in diffuse large B cell lymphoma.

Author information

1
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam, 463-707, South Korea.
2
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
3
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam, 463-707, South Korea. paikjh@snu.ac.kr.

Abstract

BACKGROUND:

Antitumor immune response of programmed cell death ligand (PD-L1) has shown clinical value not only in Hodgkin lymphoma and EBV-associated lymphomas but also in EBV-negative diffuse large B cell lymphoma (DLBCL) of non-germinal center B cell-like (non-GCB) subtype. Signal transducer and activator of transcription 3 (STAT3) is known to induce PD-L1 in immune cells and its activated form, phosphorylated STAT3 (pSTAT3), is also frequently expressed in non-GCB DLBCL. Herein, we investigated associations between PD-L1 expression/gene alteration, pSTAT3 expression and clinicopathologic variables in EBV-negative DLBCL.

METHODS:

In 107 cases of DLBCLs with non-GCB subtype (67%; 72/107), GCB subtype (25%; 27/107) and unclassifiable cases (8%; 8/107), we performed PD-L1 and pSTAT3 immunohistochemistry and fluorescence in situ hybridization for PD-L1 gene translocation and copy number gain/amplification.

RESULTS:

PD-L1 was expressed in tumor cells (PD-L1t) in 21% (23/107; 30% cutoff), immune cells (PD-L1i) in 36% (38/107; 20% cutoff), and pSTAT3 in tumor nuclei in 41% (44/107; 40% cutoff). PD-L1 gene alteration was observed in 10% (10/102) including translocation in 6% (6/102) and copy number gain/amplification in 4% (4/102). Non-GCB subtype was associated with PD-L1t and pSTAT3 (p = 0.006 and p = 0.042), and tended to have PD-L1 gene alteration (p = 0.058). Tumoral PD-L1 expression without gene alteration (PD-L1t+ GA-) correlated with pSTAT3-positive tumor cell proportions (%) (p = 0.033). In survival analysis, pSTAT3 expression independently predicted shorter PFS in total cohort (p = 0.017) and R-CHOP-treated group (p = 0.007), and in pSTAT3-negative R-CHOP-treated subset, PD-L1 expression in immune cells (PD-L1i) correlated with shorter PFS (p = 0.042).

CONCLUSIONS:

Gene alteration and protein expression of PD-L1 and pSTAT3 expression were closely related in DLBCL and constituted features of non-GCB subtype. In addition to known clinical significance of pSTAT3, immune cell expression of PD-L1 (PD-L1i) had also clinical value in pSTAT3-dependent manner. These findings may provide an insight into immunotherapeutic strategy and risk stratification in DLBCL patients.

KEYWORDS:

Diffuse large B cell lymphoma; Microenvironment; PD-L1; Prognosis; pSTAT3

PMID:
30458835
PMCID:
PMC6245852
DOI:
10.1186/s12967-018-1689-y
[Indexed for MEDLINE]
Free PMC Article

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