Cytokine Induced Killer cells effectively kill chemo-resistant melanoma cancer stem cells.

Background Metastatic Melanoma (mMel) is considered refractory to conventional chemotherapies. New molecular targeted approaches, inhibiting mutated forms of the serine-threonine kinase B-RAF, significantly increased the response rate but patients almost invariably relapse and prognosis remains severe [1,2]. Open challenge is the characterization and targeting of cancer stem cells (CSCs), considered responsible for chemoresistance and disease relapse. Adoptive immunotherapy holds great promises for the treatment of mMel and research efforts are ongoing to explore its potential activity against melanoma CSCs (mCSCs). Cytokine Induced Killer (CIK) cells are a subset of ex vivo expanded T lymphocytes with mixed CD3+CD56+ phenotype and endowed with HLA-unrestricted tumor killing activity. We and others recently reported the preclinical activity of CIK cells against several solid tumors including mMel [3]. Aim of our research is to explore the preclinical activity of CIK cells against autologous mCSCs surviving treatments with chemo or molecular targeted therapies. Conclusion: We provided first proof of concept that putative mCSCs are relatively resistant to conventional treatments with chemo or molecular targeted therapy and susceptible to immunotherapy killing by autologous CIK cells. These preclinical findings support the hypothesis that mCSC may be responsible for disease relapses and support designing of experimental immunotherapy clinical trials with CIK cells in mMel settings.