Abstract
Cancer stem cells (CSCs), also known as tumor-initiating cells, are characterized by an increased capacity for self-renewal, multipotency, and tumor initiation. While CSCs represent only a small proportion of the tumor mass, they significantly account for metastatic dissemination and tumor recurrence, thus making them attractive targets for therapy. Due to their ability to sustain in dormancy, chemo- and radiotherapy often fail to eliminate cancer cells with stemness properties. Recent advances in the understanding of the tumor microenvironment (TME) illustrated the importance of the immune contexture, determining the response to therapy and clinical outcome of patients. In this context, CSCs exhibit special properties to escape the recognition by innate and adaptive immunity and shape the TME into an immunosuppressive, pro-tumorigenic landscape. As CSCs sculpt the immune contexture, the phenotype and functional properties of the tumor-infiltrating immune cells in turn influence the differentiation and phenotype of tumor cells. In this review, we summarize recent studies investigating main immunomodulatory properties of CSCs and their underlying molecular mechanisms as well as the impact of immune cells on cancer cells with stemness properties. A deeper understanding of this bidirectional crosstalk shaping the immunological landscape and determining therapeutic responses will facilitate the improvement of current treatment modalities and the design of innovative strategies to precisely target CSCs.
Highlights
In recent years, the role of the tumor microenvironment (TME) has gained an increasing amount of attention, allowing the discovery of new concepts and development of novel therapeutic approaches
Therapeutic strategies leading to the elimination of cancer stem cells (CSCs) in addition to non-stem cancer cells may further improve the clinical outcome for tumor patients
Many of the aforementioned CSC-immune cell interactions, including the generation of M2 macrophages and Myeloid-derived suppressor cells (MDSCs), the CSC-dependent T cell suppression, the effect of IL-6 and IL-17 on the stemness properties of CSCs, and the expression of PDL1 are dependent on active signal transducer and activator of transcription 3 (STAT3) signaling in CSCs or immune cells
Summary
Luise Müller 1, Antje Tunger 1,2, Ioana Plesca 1, Rebekka Wehner , 1,2,3 Achim Temme , 2,3,4 Dana Westphal 5, Friedegund Meier 2,3,5, Michael Bachmann 2,3,6 and Marc Schmitz 1,2,3*. While CSCs represent only a small proportion of the tumor mass, they significantly account for metastatic dissemination and tumor recurrence, making them attractive targets for therapy Due to their ability to sustain in dormancy, chemo- and radiotherapy often fail to eliminate cancer cells with stemness properties. Recent advances in the understanding of the tumor microenvironment (TME) illustrated the importance of the immune contexture, determining the response to therapy and clinical outcome of patients. In this context, CSCs exhibit special properties to escape the recognition by innate and adaptive immunity and shape the TME into an immunosuppressive, pro-tumorigenic landscape.
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