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

Autor: Jeong Mi Yang, Hyun Jung Kwon, Jin Ho Paik, Jong Seok Lee, Jeong Ok Lee
Rok vydání: 2018
Předmět:
Male
STAT3 Transcription Factor
PD-L1
0301 basic medicine
Microenvironment
lcsh:Medicine
Chromosomal translocation
Kaplan-Meier Estimate
Diffuse large B cell lymphoma
B7-H1 Antigen
Disease-Free Survival
General Biochemistry
Genetics and Molecular Biology
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Immune system
Cell Line
Tumor
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
pSTAT3
Biomarkers
Tumor
medicine
Humans
Phosphorylation
Survival analysis
biology
medicine.diagnostic_test
Research
lcsh:R
General Medicine
Middle Aged
Prognosis
medicine.disease
Gene Expression Regulation
Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
biology.protein
STAT protein
Immunohistochemistry
Female
Lymphoma
Large B-Cell
Diffuse
Diffuse large B-cell lymphoma
Fluorescence in situ hybridization
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-16 (2018)
ISSN: 1479-5876
DOI: 10.1186/s12967-018-1689-y
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12967-018-1689-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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