Cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, which can invade adjoining parts of the body and spread to other organs through the bloodstream. About 90% of cancer deaths are caused by the spreading of cancer, in which the cancer cells leave the primary tumour site and enter the bloodstream. Then, the cancer cells travel into other parts of the body forming a new tumour. These single cancer cells found in the bloodstream are known as circulating tumour cells (CTCs).
CTCs were first described in 1869 by an Australian physician, Dr Thomas Ashworth. One day, he observed a blood sample from a metastatic cancer patient. Under the microscope, he discovered that the cells look identical to those of the primary tumour cell itself. Subsequently, he claimed these cells as CTCs, as they are circulating in peripheral blood. However, CTCs are very rare in the blood, even in end-stage cancer patients. Only a few CTCs relative to a background of 1 million white blood cells (WBCs) and 1 billion red blood cells (RBCs) per millilitre of peripheral blood [1].
There are two major clinical utilities of CTCs, which is included prognosis and monitoring therapeutic response. The presence of CTCs in peripheral blood is associated with decreased progression-free survival and decreased overall survival in patients with metastatic cancer. They are also used for monitoring the therapeutic response in the metastatic cancer patient. For instance, patients with persistently elevated CTCs counts suggest an ineffective therapy.
The cancer therapy to target the CTCs is chemotherapy and immunotherapy. Chemotherapy uses a drug to target rapidly dividing cells (mostly cancer cells). Immunotherapy uses biological substances to boost the immune system and improve quality of life. There are many types of immunotherapies, including monoclonal antibodies, immune checkpoint inhibitors and immune cell-based therapy. Immune cell-based therapy uses immune cells such as dendritic cells, T cells and natural killer (NK) cells to kill the tumour cells.
According to a study published in 2013, NK cells can interact with CTCs and subsequently, control tumour cells from spreading [2]. The role of NK cells involves the detection and elimination of circulating tumour cells. Based on research, depletion or dysfunction of NK cells promote new tumour formation in immunocompetent mice [3]. Another study also proved that in adoptive NK immune cell therapy elevated levels of NK cells within a short period are correlated with CTCs reduction, suggesting that the NK cells are killing CTCs within the first 24 hours [4]. Hence, NK cell-based immunotherapy is a potential therapy to target CTCs.
Click here for more information about NK immune cell-based immunotherapy:
- nkbiocell.com
References:
- Andree, K.C., van Dalum, G. and Terstappen, L.W., 2016. Challenges in circulating tumor cell detection by the CellSearch system. Molecular oncology, 10(3), pp.395-407.
- López-Soto, L. Huergo-Zapico, J.A. Galván, L. Rodrigo, A.G. de Herreros, A. Astudillo, S. Gonzalez, 2013. Epithelial–Mesenchymal Transition Induces an Antitumor Immune Response Mediated by NKG2D Receptor, The Journal of Immunology, 190 (2013) 4408.
- B. Merzoug, S. Marie, N. Satoh‑Takayama, S. Lesjean, M. Albanesi, H. Luche, H.J. Fehling, J.P.D. Santo, C.A. Vosshenrich, 2014. Conditional ablation of NKp46+ cells using a novel Ncr1greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases, European journal of immunology, 44 (2014) 3380-3391.
- Liu, Q. Chen, J. Yan, Y. Wang, C. Zhu, C. Chen, X. Zhao, M. Xu, Q. Sun, R. Deng, H. Zhang, Y. Qu, J. Huang, B. Jiang, J. Yu, 2013. MiRNA-296-3p-ICAM-1 axis promotes metastasis of prostate cancer by possible enhancing survival of natural killer cell-resistant circulating tumour cells, Cell Death & Disease, 4 (2013) e928-e928.