Recombinant antibodies from clonally expanded cancer-associated plasma cells

Although the clinical significance of plasma cells within tumors has been recognized, studies on the development of plasma cells and the characteristics of the antibodies they secrete within the tumor microenvironment remain limited. We investigated the properties of plasma cells within cancer tissues using single-cell RNA and single cell B cell receptor sequencing. We characterized plasma cells exhibiting clonal expansion and synthesized the antibodies produced by these cells, confirming the clinical relevance of immunoglobulin H (IGH) isotypes. Plasma cells comprised approximately 5% of the total immune cell population within the tumor; clonal expansion was more prevalent in plasma cells than in B cells. Among plasma cells, the most frequent immunoglobulin isotype was IGHG1 and IGKC. We synthesized six recombinant antibodies, including those from the largest clonal plasma cells. Two antibodies that formed clones showed membranous staining in cancer cells. The cancer cells that metastasized to the lymph node showed a loss of expression as observed by immunohistochemistry. Analysis of bulk RNA sequencing data from 1078 patients with breast cancer revealed that tumor-infiltrating plasma cells expressing IGHG1 were associated with favorable prognoses. These tumors exhibited increased B cell receptor diversity, immunogenic mutation, and intratumoral heterogeneity. This study suggests the potential for discovering cancer-associated antibodies derived from intratumoral plasma cells.