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Cancer Immunology, Immunotherapy

, Volume 64, Issue 1, pp 91–97 | Cite as

Cancer stem cells: perspectives for therapeutic targeting

  • Cristina Maccalli
  • Ruggero De Maria
Focussed Research Review

Abstract

Cells with “stemness” and tumor-initiating properties have been isolated from both hematological and solid tumors. These cells denominated as cancer stem cells (CSCs), representing rare populations within tumors, have the ability to metastasize and are resistant to standard therapies and immunotherapy. Heterogeneity and plasticity in the phenotype of CSCs have been described in relation to their tissue origin. Few definitive markers have been isolated for CSCs from human solid tumors, limiting their usage for in vivo identification of these cells. Nevertheless, progress in the emerging CSCs concept has been achieved gaining, at least for some type of tumors, their biological and immunological characterization. The recent identification of molecules and signaling pathways that are up-regulated or aberrantly induced in CSCs allowed the development of small agents for specifically targeting of CSCs. A general low immunogenic profile has been reported for CSCs with, in some cases, the identification of the mechanisms responsible of the impairment of cell-mediated immune responses. These concepts are discussed in the context of this review. Although CSCs still need to be fully characterized, potential candidate markers and/or signaling pathways, to be exploited for the design of novel CSC-targeting therapeutic strategies, are described in this review.

Keywords

Cancer stem cells Cancer stem cells-associated signaling pathways Immunological profile Immune modulation CSC-targeted therapies NIBIT 2013 

Abbreviations

ALDH

Aldehyde dehydrogenase

BMP4

Bone morphogenetic protein 4

COA-1

Colon antigen-1

CRC

Colorectal cancer

CSCs

Cancer stem cells

DLL4

Delta-like ligand 4

GDF-15

Growth differentiation factor-15

GBM

Glioblastoma multiforme

IFN

Interferon

mAb

Monoclonal antibody

MDR1

Multi-drug resistance 1 gene

PD-1

Programmed death 1

PGE2

Prostaglandin E2

PI3K

Phosphatidylinositide 3-kinase

PTEN

Phosphatase and tensin homolog

TGFB-1

Transforming growth factor beta 1

XIAP

X-linked inhibitor of apoptosis

Notes

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Unit of Immuno-biotherapy of Melanoma and Solid TumorsSan Raffaele Foundation CentreMilanItaly
  2. 2.NIBIT-Italian Network for Bio-therapy of Tumors, c/o Medical Oncology and ImmunotherapyAzienda Ospedaliera Universitaria SeneseSienaItaly
  3. 3.Regina Elena National Cancer InstituteRomeItaly

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