Tumor-Infiltrating B Lymphocytes: Promising Immunotherapeutic Targets for Primary Liver Cancer Treatment

SIMPLE SUMMARY: Primary liver cancer is a frequent cause of cancer-related death with high mortality rates. Cellular components of the heterogeneous tumor microenvironment (TME) play a crucial role in promoting or inhibiting tumor growth. Indeed, a multitude of immune populations, including B cells, have been found within the liver TME. This review offers a comprehensive summary of B-cell biology and maturation process, as well as their phenotypic and complex functional properties in cancer. We also summarize the prognostic impact of B lymphocytes in liver malignancies and their potential benefit in the development of new immunotherapies for primary liver cancer treatment. ABSTRACT: Hepatocellular carcinoma and cholangiocarcinoma are the fourth most lethal primary cancers worldwide. Therefore, there is an urgent need for therapeutic strategies, including immune cell targeting therapies. The heterogeneity of liver cancer is partially explained by the characteristics of the tumor microenvironment (TME), where adaptive and innate immune system cells are the main components. Pioneering studies of primary liver cancers revealed that tumor-infiltrating immune cells and their dynamic interaction with cancer cells significantly impacted carcinogenesis, playing an important role in cancer immune evasion and responses to immunotherapy treatment. In particular, B cells may play a prominent role and have a controversial function in the TME. In this work, we highlight the effect of B lymphocytes as tumor infiltrates in relation to primary liver cancers and their potential prognostic value. We also present the key pathways underlying B-cell interactions within the TME, as well as the way that a comprehensive characterization of B-cell biology can be exploited to develop novel immune-based therapeutic approaches.