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

• Published in: Oncoimmunology 2019-04, Vol.8 (4), p.e1571388
• Main Authors: Zhang, Zhao, Ma, Lijie, Goswami, Shyamal, Ma, Jiaqiang, Zheng, Bohao, Duan, Meng, Liu, Longzi, Zhang, Lijun, Shi, Jieyi, Dong, Liangqing, Sun, Yumeng, Tian, Lingyu, Gao, Qiang, Zhang, Xiaoming
• Format: Article
• Language: English
• Subjects: B cell subsets; Liver cancer; Original Research; prognosis; tumor microenvironment (TME); tyramide signal amplification (TSA)
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2019.1571388

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 − isotype-switched 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.