Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer

Szaryńska, Magdalena; Olejniczak, Agata; Kobiela, Jarosław; Łaski, Dariusz; Śledziński, Zbigniew; Kmieć, Zbigniew

doi:10.1038/s41598-018-30525-3

Cited by 35 publications

(30 citation statements)

References 91 publications

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“…Solid tumors grow in a three-dimensional (3D) spatial conformation, resulting in heterogeneous exposure to oxygen and nutrients, as well as to physical and chemical stresses, which is not mirrored in the 2D adherent systems of cancer cell cultures (43). It has been suggested that spherical cultures better mimic the cancer cell organization and development in vivo (10,12,44). Similar to solid tumors, the external layer of a sphere is composed of cells displaying high proliferation rates, the middle layer is essentially formed by senescent cells, and the core contains necrotic cells (11).…”

Section: Discussionmentioning

confidence: 99%

Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

et al. 2019

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The aim of this study was to examine the effects of 5-fluorouracil (5-FU), anti-epidermal growth factor receptor (EGFR) antibody and aspirin (ASA) on the characteristics of two CRC cell lines, HCT116 and HT29, maintained in a spherical culture system. We observed that the morphology of both the HCT116 and HT29 cell-derived spheres was significantly impaired and the size of the colonospheres was markedly reduced following treatment with the aforementioned three drugs. In contrast to adherent cultures, the spherical cultures were more resistant to the tested drugs, as was reflected by their capacity to recreate the colonospheres when sustained in serum-free medium. Flow cytometric analysis of the drug-treated HCT116 cell-derived spheres revealed changes in the fraction of cells expressing markers of cancer stem cells (CSCs), whereas the CSC phenotype of HT29 cell-derived colonospheres was affected to a lesser extent. All reagents enhanced the percentage of non-viable cells in the colonospheres despite the diminished fraction of active caspase-3-positive cells following treatment of the HT29 cell-derived spheres with anti-EGFR antibody. Increased autophagy, assessed by acridine orange staining, was noted following the incubation of the HT29-colonospheres with ASA and 5-FU in comparison to the control. Notably, the percentage of cyclooxygenase (COX)-2-positive cells was not affected by ASA, although its activity was markedly elevated in the colonospheres incubated with anti-EGFR antibody. On the whole, the findings of this study indicate that all the tested drugs were involved in different cellular processes, which suggests that they should be considered for the combined therapeutic treatment of CRC, particularly for targeting the population of CSC-like cells. Thus, cancer cell-derived spheres may be used as a preferable model for in vitro anticancer drug testing.

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Section: Discussionmentioning

confidence: 99%

Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

et al. 2019

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“…A recent study using CD133 positive, CD29 positive and CD44 positive CSCs showed that the number of activated DCs was decreased after CSC lysate/LPS (intracellular) or CSC conditioned medium/LPS (extracellular) stimulation. This result suggested that CSCs might impair the functions of DCs [49]. Although the relationship between DCs and GCSCs is still unclear, the functional DCs are required in the immune microenvironment for T cell activation.…”

Section: Gcscs and The Immune Microenvironmentmentioning

confidence: 96%

Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets

Yasuda

et al. 2020

Biomedicines

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Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) are known to be involved in chemotherapy resistance and the development of metastases. Although CSCs harbor self-renewal and tumorigenic abilities, the immune microenvironment surrounding CSCs provides various factors and supports the maintenance of CSC properties. The current review summarizes the accumulating findings regarding the relationship between the immune microenvironment and gastric CSCs (GCSCs), which will support the possibility of developing novel therapeutic strategies for targeting GCSCs.

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“…Bruttel and Wischhusen on the other hand showed that CSCs evade the immune system via lack of molecules needed for T cell recognition [ 390 ]. Several other studies showed that CSCs evade the immune system due to their creation of an immune suppressive microenvironment [ 391 , 392 ]. Despite the above, the high expression of PD-L1 on the CSCs’s surfaces makes CSCs targets of checkpoint inhibitors.…”

Section: Targeting Cancer Stem Cells In Tumor Microenvironmentmentioning

confidence: 99%

Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

Dzobo

Senthebane

Ganz

et al. 2020

Cells

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Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

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Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer

Cited by 35 publications

References 91 publications

Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets

Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

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