Phenotyping and clinical utility of phagocytic polyploid giant cancer macrophages in blood

Abstract

Historically, polyploid giant cancer cells (PGCCs) within tumors have been ignored as superfluous inflammatory refuse with no intrinsic clinical or biological relevance. However recently, multiple studies have described the existence PGCCs in solid tumor masses that appear to correlate with tumor progression, and can also appear in blood circulation as cancer associated macrophage like cells (CAMLs). In an effort to understand the clinical and biological role of CAMLs (i.e. PGCCs in circulation), we initiated a multi-institutional 2 year prospective study of patients in an array of solid tumors (n = 293; breast, prostate, esophageal, lung, pancreas, or renal cell carcinoma), finding that CAMLs significantly correlate with progression and disease spread. We further evaluated the biological traits of CAMLs isolated from patients, identifying abnormal cellular characteristics including self-renewing proliferation, proangiogenic stem cell biomarkers, with overlapping myeloid, epithelial and endothelial characteristics. Here we report that CAMLs are highly indicative of disease progression in all cancer stages and appear to mimic phenotypes associated with metastatic niche initiation (i.e. traversing blood as self-renewing multipotent myeloid cells).