title: Concise Review: Targeting Cancer Stem Cells Using Immunologic Approaches.
abstract: Cancer stem cells (CSCs) represent a small subset of tumor cells which have the ability to self-renew and generate the diverse cells that comprise the tumor bulk. They are responsible for local tumor recurrence and distant metastasis. However, they are resistant to conventional radiotherapy and chemotherapy. Novel immunotherapeutic strategies that specifically target CSCs may improve the efficacy of cancer therapy. To immunologically target CSC phenotypes, innate immune responses to CSCs have been reported using Natural killer cells and γδ T cells. To target CSC specifically, in vitro CSC-primed T cells have been successfully generated and shown targeting of CSCs in vivo after adoptive transfer. Recently, CSC-based dendritic cell vaccine has demonstrated significant induction of anti-CSC immunity both in vivo in immunocompetent hosts and in vitro as evident by CSC reactivity of CSC vaccine-primed antibodies and T cells. In addition, identification of specific antigens or genetic alterations in CSCs may provide more specific targets for immunotherapy. ALDH, CD44, CD133, and HER2 have served as markers to isolate CSCs from a number of tumor types in animal models and human tumors. They might serve as useful targets for CSC immunotherapy. Finally, since CSCs are regulated by interactions with the CSC niche, these interactions may serve as additional targets for CSC immunotherapy. Targeting the tumor microenvironment, such as interrupting the immune cell, for example, myeloid-derived suppressor cells, and cytokines, for example, IL-6 and IL-8, as well as the immune checkpoint (PD1/PDL1, etc.) may provide additional novel strategies to enhance the immunological targeting of CSCs.
authors: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.|State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, Hubei Province, People's Republic of China.
authors: Qin
authors: Q
authors: Pan
authors: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors: Qiao
authors: Q
authors: Li
authors: Department of Neurosurgery, Navy General Hospital, Beijing, People's Republic of China.
authors: Shuang
authors: S
authors: Liu
authors: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.|Department of General Surgery, General Hospital of PLA, Beijing, People's Republic of China.
authors: Ning
authors: N
authors: Ning
authors: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, Hubei Province, People's Republic of China.
authors: Xiaolian
authors: X
authors: Zhang
authors: Department of General Surgery, General Hospital of PLA, Beijing, People's Republic of China.
authors: Yingxin
authors: Y
authors: Xu
authors: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors: Alfred E
authors: AE
authors: Chang
authors: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors: Max S
authors: MS
authors: Wicha
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
keywords: Cancer stem cells; Cytotoxic T lymphocytes; Immunotherapy; Lymphocytes