Heterogeneity and Functions of Tumor-Infiltrating Antibody Secreting Cells: Lessons from Breast, Ovarian, and Other Solid Cancers.

Abstract

Simple SummaryB cells are gaining increasing recognition as important contributors to the tumor microenvironment, influencing, positively or negatively, tumor growth, patient survival, and response to therapies. Antibody secreting cells (ASCs) constitute a variable fraction of tumor-infiltrating B cells in most solid tumors, and they produce tumor-specific antibodies that can drive distinct immune responses depending on their isotypes and specificities. In this review, we discuss the current knowledge of the heterogeneity of ASCs infiltrating solid tumors and how both their canonical and noncanonical functions shape antitumor immunity, with a special emphasis on breast and ovarian cancers.Neglected for a long time in cancer, B cells and ASCs have recently emerged as critical actors in the tumor microenvironment, with important roles in shaping the antitumor immune response. ASCs indeed exert a major influence on tumor growth, patient survival, and response to therapies. The mechanisms underlying their pro- vs. anti-tumor roles are beginning to be elucidated, revealing the contributions of their secreted antibodies as well as of their emerging noncanonical functions. Here, concentrating mostly on ovarian and breast cancers, we summarize the current knowledge on the heterogeneity of tumor-infiltrating ASCs, we discuss their possible local or systemic origin in relation to their immunoglobulin repertoire, and we review the different mechanisms by which antibody (Ab) subclasses and isoforms differentially impact tumor cells and anti-tumor immunity. We also discuss the emerging roles of cytokines and other immune modulators produced by ASCs in cancer. Finally, we propose strategies to manipulate the tumor ASC compartment to improve cancer therapies.