Immune evasion by cancer stem cells

• Published in: Regenerative therapy Vol. 17; pp. 20 - 33
• Main Authors: Tsuchiya, Hiroyuki, Shiota, Goshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021; Japanese Society for Regenerative Medicine; Elsevier
• Subjects: Cancer stem cells; Immune checkpoints; Immune evasion; NK cells; Review; T cells; ETO; TAM; TAP; TCR; ULBP; KDM4; MDSC; MHC; T cells; SCID; OCT4; SOX2; DNMT; CSC; PD-L1/2; CCR7; CTLA-4; uPAR; ADCC; AML; LILR; PI9; NK cells; LAG3; NOD; NSG; CIK; MIC; Treg; Immune evasion; Immune checkpoints; ARID3B; NGF; CMV; EMT; LMP; ALDH; EV; LOX; KIR; HNSCC; PSME3; CTL; Cancer stem cells; NK; PD-1; DC; MIC, MHC class I polypeptide-related sequence; SCID, severe combined immunodeficient; NSG, NOD/SCID IL-2 receptor gamma chain null; DC, dendritic cell; NOD, nonobese diabetic; CTLA-4, cytotoxic T-cell-associated antigen-4; ULBP, UL16 binding protein; NGF, nerve growth factor; OCT4, octamer-binding transcription factor 4; CIK, cytokine-induced killer cell; LOX, lysyl oxidase; TAP, transporter associated with antigen processing; CSC, cancer stem cell; PI9, protease inhibitor 9; CTL, cytotoxic T lymphocytes; MDSC, myeloid-derived suppressor cell; ALDH, alcohol dehydrogenase; KIR, killer immunoglobulin-like receptor; uPAR, urokinase-type plasminogen activator receptor; HNSCC, head and neck squamous cell carcinoma; KDM4, lysine-specific demethylase 4C; ETO, fat mass and obesity associated protein; Treg, regulatory T cell; AML, acute myeloid leukemia; MHC, major histocompatibility complex; PSME3, proteasome activator subunit 3; LAG3, lymphocyte activation gene 3; LMP, low molecular weight protein; NK, natural killer; LILR, leukocyte immunoglobulin-like receptor; PD-L1/2, ligands 1/2; SOX2, sex determining region Y-box 2; EV, extracellular vesicle; CMV, cytomegalovirus; TAM, tumor-associated macrophage; DNMT, DNA methyltransferase; PD-1, programmed death receptor-1; ADCC, antibody-dependent cell mediated cytotoxicity; EMT, epithelial–mesenchymal transition; ARID3B, AT-rich interaction domain-containing protein 3B; CCR7, C–C motif chemokine receptor 7; TCR, T cell receptor
• ISSN: 2352-3204; 2352-3204
• DOI: 10.1016/j.reth.2021.02.006

Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies. •Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors.•Immune evasion is a fundamental feature of CSCs.•Immune evasion mechanisms must be precisely clarified to improve tumor immunotherapy.•CSCs are promising targets for tumor immunotherapy.