Immunity evolved not only to resist external challenges but also to serve in an internal, “housekeeping” function that operates in the absence of overt inflammation. Apoptotic, senescent, and neoantigen-expressing cells require clearance. In addition, routine, tempered engagement with diverse commensal microflora is essential to ensure epithelial integrity [1]. The immune system is efficient in these capacities for most of our lifespan. However, with advancing age homeostasis is challenged by genomic instability, cellular senescence, immune dysregulation, and microbiome changes, factors increasingly shown to foster the emergence of cancer [2].

The barrier role of epithelial linings and the dynamics of their renewal renders their maintenance particularly important [3]. The high mitotic activity of underlying stem cells and proximity to environmental mutagens can promote cancer in epithelial tissue [4]. Typically, cancer evolves over years with the gradual emergence, selection, and persistence of cellular variants that influence their local environment, a hallmark being the temperance of immunity [5]. This slow evolution and cellular complexity confound study of tumor microenvironment (TME) development.

The murine ID8 ovarian cancer (OvCa) model transcends these challenges as a rapidly developing carcinoma in an accessible site rich in immunomodulatory molecules and diverse immunoregulatory cells [6]. Ascites fluid, characterized as an aqueous TME, accumulates in the peritoneal cavity (PerC) as OvCa expands sharing key features found in human serous ovarian carcinoma [7], [8], [9], [10], [11]. The peritoneal cavity (PerC) is enriched for B-1 B cells that produce anti-inflammatory IL-10 and “natural” antibodies, primarily IgM, specific for commensal microflora, apoptotic cell ligands, and self-carbohydrates, glycolipids, and glycoproteins. These “innate-like” B cells serve a vital role in housekeeping and controlling inflammation yet have not been investigated in the ID8 model [12].

In this report, changes in B cell biology during OvCa are described. PerC B-1B cells were found to disappear with advancing disease. Intriguingly, spleen B-1 cells and marginal zone B (MZB) were also depleted, whereas B2 cells persisted. The concomitant loss of a thymus-independent immune responses associated with these B cell subsets confirmed their depletion rather than relocation. This selective loss could reflect the BCR specificity of these subsets and their limited potential for self-renewal [13]. The results are discussed in the context of the stress placed on innate humoral immunity during ovarian cancer.