Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

Donini, Chiara; Rotolo, Ramona; Proment, Alessia; Sangiolo, Dario; Leuci, Valeria

doi:10.3390/cells10030543

Cited by 17 publications

(30 citation statements)

References 228 publications

(171 reference statements)

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“…Furthermore, activation of type I IFN should increase the expression of MHC molecules, and therefore makes CSCs recognizable by the adaptive immunity. We can also envisage that, although CSCs are able to resist drug-mediated damage, pharmacological treatments could, in any case, have an impact by causing the upregulation of molecules belonging to a “stress signature”; these stress molecules may serve as activating ligands for cytotoxic immune cells, such as Natural Killers (Tallerico et al 2016 ; Donini et al 2021 ).…”

Section: Main Textmentioning

confidence: 99%

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

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Myeloid cells infiltrating tumors are gaining ever growing attention in the last years because their pro-tumor and immunosuppressive functions are relevant for disease progression and therapeutic responses. The functional ambiguity of tumor-associated macrophages (TAMs), mostly promoting tumor evolution, is a challenging hurdle. This is even more evident in the case of cancer stem cells (CSCs); as active participants in the specialized environment of the cancer stem cell niche, TAMs initiate a reciprocal conversation with CSCs. TAMs contribute to protect CSCs from the hostile environment (exogenous insults, toxic compounds, attacks from the immune cells), and produce several biologically active mediators that modulate crucial developmental pathways that sustain cancer cell stemness. In this review, we have focused our attention on the interaction between TAMs and CSCs; we describe how TAMs impact on CSC biology and, in turn, how CSCs exploit the tissue trophic activity of macrophages to survive and progress. Since CSCs are responsible for therapy resistance and tumor recurrence, they are important therapeutic targets. In view of the recent success in oncology obtained by stimulating the immune system, we discuss some macrophage-targeted therapeutic strategies that may also affect the CSCs and interrupt their malevolent alliance.

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Section: Main Textmentioning

confidence: 99%

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

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“…However, many factors affect CRC immunotherapy, among which cancer stem cells are a key factor that might result in immunotherapy failure. Although the association of cancer stem cells with the immune system has not been well investigated because of experimental limitations (Donini et al, 2021), evidence demonstrates that cancer stem cells have a modulatory effect on the immune system in CRC patients (Xu et al, 2018). In this study, we showed that the stemness scores were significantly associated with the TME, including the immune, stromal scores, and tumor purity, and that they greatly correlated with some TIICs.…”

Section: Discussionmentioning

confidence: 56%

Integrative Analysis Revealed Stemness Features and a Novel Stemness-Related Classification in Colorectal Cancer Patients

Yin

et al. 2022

Front. Cell Dev. Biol.

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Cancer stem cells play crucial roles in colorectal cancer (CRC) tumorigenesis and treatment response. This study aimed to determine the value of the mRNA stemness index (mRNAsi) in CRC and introduce a stemness-related classification to predict the outcome of patients. mRNAsi scores and RNA sequence data of CRC patients were analyzed. We found that high mRNAsi scores were related to early-stage CRC and a better patient prognosis. Two stemness-based subtypes (subtype I and II) were identified. Patients in subtype I presented a significantly better prognosis than those in subtype II. Patients in these two subtype groups presented significantly different tumor immunity scores and immune cell infiltration patterns. Genomic variations revealed that patients in subtype I had a lower tumor mutation burden than those in subtype II. A three-gene stemness subtype predictor was established, showing good diagnostic value in discriminating patients in different subtypes. A prognostic signature based on five stemness-related genes was established and validated in two independent cohorts and clinical samples, showing a better predictive performance than other clinical parameters. We concluded that mRNAsi scores were associated with the clinical outcome in CRC patients. The stemness-related classification was a promising prognostic predictor for CRC patients.

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“…Another key factor regulating innate immunity is the stimulator of interferon genes (STING), which also leads to the production of immune-stimulating cytokines [ 200 ]. Activation of TLRs and STING can induce good antitumor effects in the body [ 201 , 202 , 203 ]. On the basis of these results, TLR and STING agonists are being used in CSC treatment trials in combination with other chemotherapy and immunotherapies ( Figure 2 ) [ 202 , 203 ].…”

Section: Therapeutic Strategies Targeting Cscs and Tamsmentioning

confidence: 99%

“…Activation of TLRs and STING can induce good antitumor effects in the body [ 201 , 202 , 203 ]. On the basis of these results, TLR and STING agonists are being used in CSC treatment trials in combination with other chemotherapy and immunotherapies ( Figure 2 ) [ 202 , 203 ].…”

Section: Therapeutic Strategies Targeting Cscs and Tamsmentioning

confidence: 99%

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells

Luo

Yang

et al. 2022

Biomolecules

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Cancer stem cells (CSCs) are a subset of highly tumorigenic cells in tumors. They have enhanced self-renewal properties, are usually chemo-radioresistant, and can promote tumor recurrence and metastasis. They can recruit macrophages into the tumor microenvironment and differentiate them into tumor-associated macrophages (TAMs). TAMs maintain CSC stemness and construct niches that are favorable for CSC survival. However, how CSCs and TAMs interact is not completely understood. An understanding on these mechanisms can provide additional targeting strategies for eliminating CSCs. In this review, we comprehensively summarize the reported mechanisms of crosstalk between CSCs and TAMs and update the related signaling pathways involved in tumor progression. In addition, we discuss potential therapies targeting CSC–TAM interaction, including targeting macrophage recruitment and polarization by CSCs and inhibiting the TAM-induced promotion of CSC stemness. This review also provides the perspective on the major challenge for developing potential therapeutic strategies to overcome CSC-TAM crosstalk.

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Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

Cited by 17 publications

References 228 publications

Macrophages and cancer stem cells: a malevolent alliance

Macrophages and cancer stem cells: a malevolent alliance

Integrative Analysis Revealed Stemness Features and a Novel Stemness-Related Classification in Colorectal Cancer Patients

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells

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