Presence and clinical significance of tumor cells with macrophage phenotype in dif-fuse large B-cell lymphoma
10.13315/j.cnki.cjcep.2025.02.005
- VernacularTitle:弥漫大B细胞淋巴瘤中存在巨噬细胞表型的肿瘤细胞并具有临床意义
- Author:
Huihui LI
1
;
Liang ZHANG
;
Zhouyi XU
;
Wei WANG
;
Zhe WANG
Author Information
1. 中国科学技术大学附属第一医院(安徽省立医院)病理科,合肥 230036
- Publication Type:Journal Article
- Keywords:
diffuse large B-cell lymphoma;
macrophage phenotype B cell;
immunofluorescence
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(2):162-170
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the presence,proportion,clinical significance and origin of tumor cells with a macrophage phenotype in tumor tissues of patients with diffuse large B-cell lymphoma(DLBCL),and to explore wheth-er CD68 positive tumor cells can be induced in DLBCL cell lines in vitro.Methods The presence of CD68+CD163+CD20+PAX5-cells in the samples of DLBCL patients was first qualitatively detected by multiplex immunofluorescence staining,and then the proportion of CD79a+B lymphocytes,CD68+macrophages,and CD68+CD79a+double-positive cells were quantified.Patients were grouped according to the proportion of double-positive cells,and the differences in prognosis and clinicopathological features of DLBCL patients between subgroups were investigated.For cases with posi-tive BCL6 gene locus breaks,co-localization of CD68 with BCL6 gene breakapart was performed using combined immu-nofluorescence and immunological in situ hybridization to ascertain the tumor nature of B cell with a macrophage pheno-type.DLBCL cell lines(OCI-LY3,SU-DHL2)were treated with phorbol myristate acetate(PMA),and changes in the proteins levels of CD68 and PAX5 proteins were detected by flow cytometry.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA levels of PAX5,an important transcription factor for B cell differentiation and develop-ment,and macrophage-related genes(CD68,ARG1,CD163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ).In ad-dition,PMA-treated DLBCL cell lines(OCI-LY3,SU-DHL2)were co-incubated with pH-sensitive fluorescent dye pHrodo to detect the phagocytosis ability of PMA-treated DLBCL cells.Results The percentage of CD68+B lympho-cytes in 50 patients with DLBCL varied from 0 to 9.3％,and the overall survival(OS)ranged from 0.008 2 to 4.2 years.Patients with the low CD68+B lymphocytes group exhibited a significantly lower OS compared to those in the high CD68+B lymphocytes group(P=0.039).There was a significant difference in the molecular typing of DLBCL patients(P=0.009 5)between different subgroups for the proportion of CD68+B lymphocytes.CD68+B lymphocytes were derived from tumor cells in DLBCL patients.The proportion of CD68+cells and CD68+PAX5-cells significantly increased in DLBCL after treatment with PMA(P＜0.05).The other macrophage markers CD68,ARG1,CD 163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ,and the important B-cell transcription factor PAX5 were significantly different from the control group in terms of relative mRNA expression(P＜0.05).Cellular phagocytosis was enhanced after PMA treatment of DLBCL cells.Conclusion Diffuse large B-cell lymphoma tumor tissue contains a certain per-centage of CD68+neoplastic B lymphocytes.The proportion of CD68+B lymphocytes is correlated with patient progno-sis and molecular typing.DLBCL cell lines can be induced to differentiate into CD68+tumor cells in vitro.
