Circulating Cancer-Associated Macrophage-Like Cells Differentiate Malignant Breast Cancer and Benign Breast Conditions

Abstract

Background Blood based testing can be used as a non-invasive method to recover and analyze circulating tumor derived cells for clinical use. Circulating Cancer Associated Macrophage-Like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation. Methods We report on two related but separate studies: 1) CellSieve™ microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n=41). Prevalence and specificity was compared against healthy volunteers (n=16). 2) A follow-up double blind pilot study was conducted on women (n=41) undergoing core needle biopsy to diagnose suspicious breast masses. Results CAMLs were found in 93% of known malignant patients (n=38/41), averaging 19.4 cells/sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n=15/17) and 26% with benign breast conditions (n=5/19). Conclusion These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals. Impact We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage.

Sequential Tracking of PD-L1 Expression and RAD50 Induction in Circulating Tumor and Stromal Cells of Lung Cancer Patients Undergoing Radiotherapy

“…S1; refs. 1, 6, 12) using preestablished cytologic features described previously (6,11,14). An Olympus BX54WI Fluorescent microscope with Carl Zeiss AxioCam and Zen2011 Blue (Carl Zeiss) was used for all imaging.…”

“…We have previously described the defining characteristics of the two most common CTC subtypes found in cancer patients (PDCTCs and EMTCTCs), and for CAML identification (1,6,(10)(11)(12)(13)(14). For this study, only intact PDCTCs, EMTCTCs, and CAMLs were characterized ( Fig.…”

“…Recently, we have identified a prevalent CStC subtype, cancerassociated macrophage-like cells (CAMLs), using a nonaffinity microfiltration-based method that captures both CTCs and CAMLs and allows for parallel analysis of these cancer-specific circulating cell subtypes (1,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). CAMLs are recently defined circulating myeloid-derived stromal cells, found in all the stages of invasive malignancy and in various solid malignancies [e.g., breast, prostate, non-small cell lung carcinoma (NSCLC), and pancreatic; refs.…”

“…CAMLs are recently defined circulating myeloid-derived stromal cells, found in all the stages of invasive malignancy and in various solid malignancies [e.g., breast, prostate, non-small cell lung carcinoma (NSCLC), and pancreatic; refs. 11,13,14,17]. CAMLs are defined by their CD45/CD14 positivity and giant size phenotype (11,13,14,17).…”

“…11,13,14,17]. CAMLs are defined by their CD45/CD14 positivity and giant size phenotype (11,13,14,17). Although CAMLs appear to be cancer specific and disseminate from the organ sites of malignancy, it remains unknown whether they actually reside at the primary tumor site or whether they possess clinical utility.…”