Identification of B cell antigens in solid cancer: Initial insights and functional implications

Min Yao ^1* Jung-In Yang ² Philip Moresco ^2,3 Douglas Fearon ^1,2*

• ¹ Weill Cornell Medicine, Cornell University, New York, United States
• ² Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States
• ³ Stony Brook University, Stony Brook, New York, United States

Cancer antigen discovery has mostly focused on T cell antigens, while antigens driving B cell responses have been largely overlooked despite representing another important branch of adap-tive immune responses in cancer. Traditional B cell antigens in cancer have been studied using serological approaches analyzing polyclonal antibodies in serum. With recent technological ad-vances in single-cell sequencing, a few studies have begun to investigate single B cell antigen specificity in the tumor microenvironment using immunoglobulin single-cell sequencing, recombi-nant monoclonal antibody production, cancer binding screening, and antigen identification. In this review, we highlight the initial insights into B cell directed cancer antigens and categorize them into cancer-associated viral antigens and non-viral antigens, with the latter featuring autoantigens. We will further discuss the functions of B cells in cancer in the context of their antigen specificity, and categorize their functions into antibody effector function, T cell activation, and B cell secre-tion. Lastly, we will provide perspectives on the challenges and opportunities in the identification of new B cell cancer antigens and highlight their translational potential.