The Immune Privilege of Cancer Stem Cells: A Key to Understanding Tumor Immune Escape and Therapy Failure

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Sep 28

PMID 34572009

Citations 32

Authors

Claudia Galassi

Martina Musella

Nicoletta Manduca

Ester Maccafeo

Antonella Sistigu

Affiliations

Soon will be listed here.

Abstract

Cancer stem cells (CSCs) are broadly considered immature, multipotent, tumorigenic cells within the tumor mass, endowed with the ability to self-renew and escape immune control. All these features contribute to place CSCs at the pinnacle of tumor aggressiveness and (immune) therapy resistance. The immune privileged status of CSCs is induced and preserved by various mechanisms that directly affect them (e.g., the downregulation of the major histocompatibility complex class I) and indirectly are induced in the host immune cells (e.g., activation of immune suppressive cells). Therefore, deeper insights into the immuno-biology of CSCs are essential in our pursuit to find new therapeutic opportunities that eradicate cancer (stem) cells. Here, we review and discuss the ability of CSCs to evade the innate and adaptive immune system, as we offer a view of the immunotherapeutic strategies adopted to potentiate and address specific subsets of (engineered) immune cells against CSCs.

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References

Yao Y, Wang X, Jin K, Zhu J, Wang Y, Xiong S . B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subset of brain tumor stem-like cells. J Neurooncol. 2008; 89(2):121-9. DOI: 10.1007/s11060-008-9601-x. View

Mirzaei R, Sarkar S, Dzikowski L, Rawji K, Khan L, Faissner A . Brain tumor-initiating cells export tenascin-C associated with exosomes to suppress T cell activity. Oncoimmunology. 2018; 7(10):e1478647. PMC: 6169571. DOI: 10.1080/2162402X.2018.1478647. View

Dahan P, Martinez Gala J, Delmas C, Monferran S, Malric L, Zentkowski D . Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance. Cell Death Dis. 2014; 5:e1543. PMC: 4260760. DOI: 10.1038/cddis.2014.509. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Deng Z, Wu Y, Ma W, Zhang S, Zhang Y . Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015; 16:1. PMC: 4318439. DOI: 10.1186/s12865-014-0064-x. View

Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T . Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells. Cancer Sci. 2014; 105(4):389-95. PMC: 4317808. DOI: 10.1111/cas.12362. View

Raghavan S, Mehta P, Xie Y, Lei Y, Mehta G . Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J Immunother Cancer. 2019; 7(1):190. PMC: 6642605. DOI: 10.1186/s40425-019-0666-1. View

Gilbert L, Hemann M . DNA damage-mediated induction of a chemoresistant niche. Cell. 2010; 143(3):355-66. PMC: 2972353. DOI: 10.1016/j.cell.2010.09.043. View

Quesnel B . Tumor dormancy and immunoescape. APMIS. 2008; 116(7-8):685-94. DOI: 10.1111/j.1600-0463.2008.01163.x. View

10.

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

11.

Signore M, Ricci-Vitiani L, De Maria R . Targeting apoptosis pathways in cancer stem cells. Cancer Lett. 2011; 332(2):374-82. DOI: 10.1016/j.canlet.2011.01.013. View

12.

Andtbacka R, Kaufman H, Collichio F, Amatruda T, Senzer N, Chesney J . Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015; 33(25):2780-8. DOI: 10.1200/JCO.2014.58.3377. View

13.

Stein R, Ebert S, Schlahsa L, Scholz C, Braun M, Hauck P . Cognate Nonlytic Interactions between CD8 T Cells and Breast Cancer Cells Induce Cancer Stem Cell-like Properties. Cancer Res. 2019; 79(7):1507-1519. DOI: 10.1158/0008-5472.CAN-18-0387. View

14.

Benteyn D, Van Nuffel A, Wilgenhof S, Corthals J, Heirman C, Neyns B . Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed Res Int. 2013; 2013:976383. PMC: 3581259. DOI: 10.1155/2013/976383. View

15.

Maugeri-Sacca M, Zeuner A, De Maria R . Therapeutic targeting of cancer stem cells. Front Oncol. 2012; 1:10. PMC: 3356019. DOI: 10.3389/fonc.2011.00010. View

16.

Vitale I, Sistigu A, Manic G, Rudqvist N, Trajanoski Z, Galluzzi L . Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy. Trends Cell Biol. 2019; 29(5):396-416. DOI: 10.1016/j.tcb.2019.01.003. View

17.

Chen H, Joalland N, Bridgeman J, Alchami F, Jarry U, Khan M . Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8 T cells. Immunol Cell Biol. 2017; 95(7):620-629. PMC: 5550559. DOI: 10.1038/icb.2017.21. View

18.

Chang S . T helper 17 (Th17) cells and interleukin-17 (IL-17) in cancer. Arch Pharm Res. 2019; 42(7):549-559. DOI: 10.1007/s12272-019-01146-9. View

19.

Xu Y, Dong X, Qi P, Ye Y, Shen W, Leng L . Sox2 Communicates with Tregs Through CCL1 to Promote the Stemness Property of Breast Cancer Cells. Stem Cells. 2017; 35(12):2351-2365. PMC: 5958902. DOI: 10.1002/stem.2720. View

20.

Manic G, Sistigu A, Corradi F, Musella M, De Maria R, Vitale I . Replication stress response in cancer stem cells as a target for chemotherapy. Semin Cancer Biol. 2018; 53:31-41. DOI: 10.1016/j.semcancer.2018.08.003. View