163P - Tumorspheres cultured from circulating cancer stem cells overexpress the innate checkpoint CD47 in breast cancer patients

Background

Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies reported that increased expression of CD47 enable cancer cells to evade phagocytosis by macrophages and promote the cancer stem cell phenotype. Understanding the mechanisms behind this CD47 overexpression in cancer stem cells is critical for developing more effective immunotherapy. Therefore, in the current study, we evaluated the incidence and clinical relevance of tumorspheres cultured from cCSCs expressing CD47 in breast cancer patients.

Methods

110 patients with breast cancer in different stages of disease were included in this study. The determination of cCSCs was performed using the sphere-forming assay. Additionally, anti-CD47 antibody staining was applied to examine CD47 expression on breast tumorspheres.

Results

We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres was associated with disease progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100μl blood, p<0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100μl blood, p<0.05). CD47 was highly expressed in tumorspheres, which are enriched from circulating cancer stem cells and associated with triple-negative tumors. We also observed high heterogeneity of CD47 expression between the tumorspheres of a patient and between the patients.

Conclusions

The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with high expression of CD47 might suggest their immunregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may improve outcome especially in high-risk patients in part by attacking cCSCs and disinhibiting innate immunity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.