Circulating giant macrophages as a potential biomarker of solid tumors

Abstract

Significance Using microfiltration as a liquid biopsy for the recovery of circulating tumor cells (CTCs) has revealed an accompanying macrophage subset that we use as a highly sensitive biomarker for solid tumors. We supply evidence that this circulating giant cell is a subset of disseminated tumor-associated macrophages capable of binding CTCs in peripheral blood of cancer patients. The presence of this cell expands the concept of using a liquid biopsy not only to indicate cancer presence but also to track cancer treatment effects sequentially using other circulating blood cells. Further, we supply observational evidence hypothesizing a metastasis pathway model in which CTCs migrate with pro-angiogenic macrophages, linking cancer cell intravasation, migration, and extravasation and the formation of metastatic microenvironments.

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.…”