Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma

Abstract

As a major cellular component in tumor microenvironment, the distribution, frequency, and prognostic significance of infiltrating B cell subsets in hepatocellular carcinoma (HCC) remain controversial. Using tyramide signal amplification (TSA) based fluorescent multiplexed immunohistochemistry in situ, we evaluated the distribution and frequency of B cell subsets in two independent HCC cohorts (n = 619). The results were further confirmed by flow cytometry. Correlations of B cell subsets with clinicopathologic features and patient prognosis were analyzed. Five B cell subsets were defined by multiplexed immunohistochemistry and each subset was clearly separated by t-SNE dimension reduction analysis. Notably, the densities of all B cell subsets were significantly decreased in the tumor. The frequency of plasma cells within B cells was most abundant in the tumor. In training cohort (n = 258), high densities of tumor-infiltrating CD20 + B cells, naive B cells, IgM + memory B cells, CD27 − isotypeswitched memory B cells, and plasma cells were associated with superior survival. Multivariate analysis further identified CD20 + B cells, naive B cells, and CD27 − isotype-switched memory B cells as independent prognosticators for survival. Unsupervised cluster analysis confirmed increased B cell subsets harbored superior survival. In addition, high density of B cells was correlated with smaller tumor size and well differentiation. The results were validated in the independent cohort of 361 HCC patients. Intratumor infiltration of B cells is significantly impaired during HCC progression. High densities of tumor-infiltrating B cells imply a better clinical outcome. Therapies designed to target B cells may be a novel strategy in HCC.

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer

“…Naive B cells represent one of the differentiation stages of B cells, which is one of the mechanisms of autoimmune tolerance. Similar to our results, Zhang et al also found that naive B cells were associated with superior survival of LIHC patients. Eosinophils are components of the immune microenvironment that modulate tumor initiation and progression, playing an antitumorigenic role in gastric, colorectal, and many other cancers .…”

Single-Cell RNA-Seq Analysis Reveals Microenvironmental Infiltration of Plasma Cells and Hepatocytic Prognostic Markers in HCC With Cirrhosis

“…The immune microenvironment of HCC is a mixture of heterogeneous immune components (7,8), immune cells migrate from the hematopoietic organ to the liver, establish an active immune niche that interacts with stromal cells, and affect differentiation, tumorigenesis and development. Therefore, it is important to explore the composition and state of immune cells during tumorigenesis.…”

“…Indeed, the majority of patients worldwide with HCC have underlying cirrhosis (12). On a global basis, some common risk factors lead to inflammatory fibrosis or cirrhosis, accompanied by extensive immune infiltration, which is considered to be a key factor in the development and progression of HCC (7).…”

Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma of different genders

“…They respond to reencountered antigens by forming germinal centers (GC) and rapidly producing antibodies [47]. It is reported that high density of tumor-in ltrating memory B cells is closely related to superior survival [48][49][50]. In our study, the density of memory B cells in TME of female patients with LUAD was signi cantly higher than that in TME of male patients (Fig.…”