Peer-review started: January 22, 2015
First decision: March 6, 2015
Revised: May 20, 2015
Accepted: July 16, 2015
Article in press: July 17, 2015
Published online: July 27, 2015
An important percentage of colorectal cancer (CRC) patients will develop metastasis, mainly in the liver, even after a successful curative resection. This leads to a very high mortality rate if metastasis is not detected early on. Disseminated cancer cells develop from metastatic stem cells (MetSCs). Recent knowledge has accumulated about these cells particularly in CRC, so they may now be tracked from the removed primary tumour. This approach could be especially important in prognosis of metastasis because it is becoming clear that metastasis does not particularly rely on testable driver mutations. Among the many traits supporting an epigenetic amplification of cell survival and self-renewal mechanisms of MetSCs, the role of many immune cell populations present in tumour tissues is becoming clear. The amount of tumour-infiltrating lymphocytes (T, B and natural killer cells), dendritic cells and some regulatory populations have already shown prognostic value or to be correlated with disease-free survival time, mainly in immunohistochemistry studies of unique cell populations. Parallel analyses of these immune cell populations together with MetSCs in the primary tumour of patients, with later follow-up data of the patients, will define the usefulness of specific combinations of both immune and MetSCs cell populations. It is expected that these combinations, together to different biomarkers in the form of an immune score, may predict future tumour recurrences, metastases and/or mortality in CRC. It will also support the future design of improved immunotherapeutic approaches against metastasis.
Core tip: Metastasis relies on differentiation of some cancer stem cells in the primary tumour niche led by many micro-environmental signals. These signals include the participation of immune cell subsets such as tumour-infiltrating lymphocytes, dendritic cells and regulatory populations. Metastatic stem cells can be identified in the removed primary tumour. The study of the number and function of these immune cell populations in parallel with metastatic stem cells (MetSCs) in the primary tumour, together with follow-up data of patients, will define the usefulness of specific immune and MetSCs cell population combinations. This can be combined with defining new biomarkers as future predictors of tumour recurrences, metastases and/or mortality in colorectal cancer.