Abstract
The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines. We found that the detailed configuration of CSC-like markers significantly influenced the maturation and activation of DCs after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented the opposite impact on treated DCs as showed by many significant correlations. The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in tumor sample the lower number of activated DCs evidenced after stimulation. Moreover, our results showed superiority of the spherical culture model over the adherent one since spherical HCT116 and HT29 cells presented similar influence on DCs properties as CRC patients cancer cells. We concluded that the DCs features may depend directly on the properties of CSCs affected by progression status of tumor.
Highlights
Colorectal cancer (CRC) is one of the most frequent malignancies and the fourth most common cause of cancer-related deaths in the world with 1.2 million new cases being diagnosed every year
At the same time we wanted to highlight the fact that our functional tests were conducted with cells, tumor conditioned medium (TCM) or lysates obtained from third passage, the phenotypic analyses showed that cancer stem cells (CSCs) along the expansion were stable what is presented in supplementary figures (Figs S1, S2, S3)
We found that factors derived from adherent cultures of HCT116 and HT29 cells significantly decreased the proportion of FasL+ Dendritic cells (DC) in comparison to immature DCs (iDCs) (Fig. 6), what suggested that these samples exerted the inhibitory effect referring to this DC feature
Summary
Colorectal cancer (CRC) is one of the most frequent malignancies and the fourth most common cause of cancer-related deaths in the world with 1.2 million new cases being diagnosed every year. The CSC-specific immune responses in breast cancer and glioblastoma[8,9,10] were proved; despite the immune evasion of the CSCs. Vaccination of dendritic cells (DCs) with irradiated glioma tumorspheres was demonstrated to increase the survival rate in a mice cancer model[9]. Studies conducted on tumorospheres derived from various types of cancers, including breast[43,44,45], colon[11,12,37,39,46], lung[47,48] and prostate[49] cancer as well as glioma[8] and melanoma[50] showed that sphere-based assays could be a reliable platform for development of immunotherapy targeting CSCs. It is believed that spherical cultures can provide short-term patient-derived CSCs for the evaluation of DC-based therapies what defined the main goals of our study
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