American Association for Cancer Research
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10780432ccr123497-sup-fig4.pdf (498.42 kB)

Supplementary Figure 4 from Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

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posted on 2023-03-31, 17:37 authored by Jie-Yi Shi, Qiang Gao, Zhi-Chao Wang, Jian Zhou, Xiao-Ying Wang, Zhi-Hui Min, Ying-Hong Shi, Guo-Ming Shi, Zhen-Bin Ding, Ai-Wu Ke, Zhi Dai, Shuang-Jian Qiu, Kang Song, Jia Fan

PDF file - 498K, Representative flow cytometry data showing that percentages of granzyme B+ and TRAIL+ cells in total CD20+ cells are significantly higher in MIL-Bs than in PIL-Bs, respectively (n=5).

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ARTICLE ABSTRACT

Purpose: The role of infiltrating B cells in hepatocellular carcinoma has been overlooked for many years. This study is aimed to delineate the distribution, prognostic value, and functional status of B cells in human hepatocellular carcinoma.Experimental design: Immunohistochemistry was used to investigate the distribution and clinical significance of infiltrating CD20+ B cells in a series of 120 patients with hepatocellular carcinoma. The results were further tested in an independent series of 200 patients with hepatocellular carcinoma. The functional status of CD20+ B cells was determined by flow cytometry, immunofluorescence, and in vitro coculture assay.Results: Infiltrating CD20+ B cells were predominantly concentrated in the tumor invasive margin, compared with the peri- and intratumor areas. High density of margin-infiltrating B lymphocytes (MIL-B) positively correlated with small tumor size, absence of vascular invasion, and increased density of CD8+ T cells (P < 0.05). Survival analyses revealed that increased number of MIL-Bs and their penetration through the tumor capsule were significantly associated with improved overall and recurrence-free survival, and were identified as independent prognosticators for patients with hepatocellular carcinoma (P < 0.05). Importantly, the results were further validated in another independent hepatocellular carcinoma cohort. Moreover, we found that MIL-Bs featured an atypical memory phenotype (IgD−IgG+CD27−CD38−), expressed surface markers characteristic of antigen-presenting cells, possessed tumor-killing potential by producing IFN-γ, interleukin 12p40 (IL-12p40), granzyme B, and TRAIL, and acted in cooperation with CD8+ T cells.Conclusions: The profile of CD20+ B cells in situ is a new predictor of prognosis for patients with hepatocellular carcinoma and provides a novel target for an optimal immunotherapy against this fatal malignancy. Clin Cancer Res; 19(21); 5994–6005. ©2013 AACR.