Immunotherapy of cancer stem cells in solid tumors: initial findings and future prospective.
BACKGROUND
Conventional chemotherapies seemed to have reached a therapeutic plateau in the treatment of solid tumors and many metastatic diseases are still incurable. Events of chemo-resistance and relapses appear to be sustained by a subset of putative cancer stem cells (CSCs). New anticancer strategies need to face this new challenge exploring their efficacy against CSCs. Immunotherapy has raised enthusiasms in cancer therapy and its potential against CSCs is an intriguing field of research.


METHODS
In this work we reviewed the immunotherapy approaches directed against CSCs in solid tumors. We schematically divided adaptive immunotherapy strategies, mainly based on dendritic cell-vaccination, and strategies exploiting MHC-unrestricted effectors like natural killer cells, γδ T lymphocytes and cytokine-induced killer cells. Findings, strength and limitations of these models are discussed and compared highlighting their potential clinical relevance.


CONCLUSIONS
The important biologic role and clinical relevance of CSCs introduced a 'noble target' for immunotherapy and cancer treatments in general. Initial evidences suggest that CSCs may be susceptible to various types of immunotherapy attacks, overcoming their chemo-resistance. Investigation of important safety issues, based on shared features with 'normal' stem cells, along with intriguing synergisms with modulatory agents are open challenges for the next future and effective clinical translation.
Candiolo Cancer Institute-FPO, IRCCS , Candiolo, 10060 , Italy.
Loretta
L
Gammaitoni
Valeria
V
Leuci
Giulia
G
Mesiano
Lidia
L
Giraudo
Maja
M
Todorovic
Fabrizio
F
Carnevale-Schianca
Massimo
M
Aglietta
Dario
D
Sangiolo
D000818:Animals; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation; D003713:Dendritic Cells / Q000637:transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D016219:Immunotherapy, Adoptive / Q000379:methods / Q000639:trends; D007694:Killer Cells, Natural / Q000637:transplantation; D008285:Major Histocompatibility Complex / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000637:transplantation
cancer immunotherapy; cancer stem cells; cell therapy; solid tumors