Circulating tumor cells (CTCs) are released from primary tumors to the circulations and metastatic site. CTCs have attracted attention as cause of metastasis and therapeutic predictive marker. Epithelial marker EpCAM and cytokeratins are used to capture these CTCs, however, the existing approaches are hampered by the reasons that CTCs may undergo epithelial-mesenchymal transition (EMT), which is characterized by down-regulation of epithelial markers, including EpCAM and cytokeratins. Therefore, it is needed to find a new EMT-induced CTC marker and methods. In this review, we focused on the EMT-induced CTC detection methods and new CTC detection technologies using micro-fluid devices including CTCchip.
The maintenance and repair of many adult tissues are ensured by stem cells, which reside at the top of the cellular hierarchy of the tissues. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation. Cancer stem cells (CSCs) have common features with normal stem cells regarding the ability of self-renewal and differentiation into diverse cells. CSCs are considered to be responsible for the poor prognosis of various types of cancers as they are related to therapeutic resistance and recurrence. Therefore elucidation of molecular mechanisms of CSCs is very important to conquer unresectable cancers via development of CSC targeted therapies. However, little is known about the molecular mechanisms of CSCs because rarity of CSCs in cancer tissues hinders the research on CSCs. The origin of CSCs and how CSCs acquire their properties are still to be elucidated. This review summarized the properties of CSCs and referred to the current issues of CSC researches. We also introduced our method of inducing colon CSC properties by defined factors and collecting them with cell sorter. This method probably overcomes the quantitative limitations of CSCs, and provides us a better understanding of molecular mechanisms of CSCs, leading to developing new CSC targeted therapy.
PD-1/PD-L1 immune checkpoint pathway, which maintains self-tolerance and limits collateral tissue damage in a physiological state, can be co-opted by cancer cells to evade immune surveillance. Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, can unleash anti-tumor immunity and mediate durable cancer regression. However, the complex biology of this pathway has not been fully elucidated, including the genetic basis of PD-L1 upregulation in cancer. Recently, we have identified a novel genetic mechanism of immune evasion associated with structural variations (SVs) disrupting the 3’-untranlated region (UTR) of the PD-L1 gene in a variety of cancers. Despite a large diversity in SV type, these SVs are invariably associated with a marked increase of PD-L1 expression, which promotes tumor progression and immune escape. Here we present an overview of PD-1/PD-L1 immune checkpoint blockade therapy, and highlight the genetic mechanisms of PD-L1 activation, including copy number amplification, promoter replacement, as well as 3’-UTR disruption, with a special focus on their relevance as a biomarker.
Both free alpha-galactosylceramide (αGalCer) and αGalCer loaded dendritic cells (DCG) activate invariant NaturalKiller T (iNKT) cells. Interestingly, although both free αGalCer and DCG treatment induce liver injury, DCG treatment doesn’t cause lethal liver injury compared with free αGalCer treatment. DCG may be able to activate iNKT cells directly in vivo. On the other hand, free αGalCer are taken by CD1d-positive cells and CD1d-positive cells present CD1d-αGalCer complex for iNKT cells in vivo. Specialized antigen-presenting cells such as dendritic cells may play antigen presentation for iNKT cells, however, how other CD1d positive cells participate in this reaction is not clear. Using CD31 antibody and sorting technique, we separate CD31 negative hepatocyte (HC) and CD31 positive endothelial cells (EC). Both CD31 negative HC and CD31 positive EC are CD1d-positive cells. We showed that CD31 positive EC were more injured after free αGalCer treatment than after DCG treatment. Moreover, EC from mice treated with free αGalCer induced naïve hepatic lymphocyte to produce TNF, which play pivotal role in liver injury by both free αGalCer and DCG treatment, and EC from mice treated with DCG did not. These results indicate that EC play antigen presentation for iNKT cells after free αGalCer treatment and injury of EC may relate to lethal liver injury.
Myeloid derived suppressor cells (MDSCs), a major player for tumor-induced immunosuppression, especially induce antigen-specific CD8-Tcell tolerance and contribute to tumor growth and progression. MDSCs represent a heterogeneous group of cells originated from the myeloid cells. MDSCs accumulate in tumor-bearing mice and cancer patients. Various drugs that directly target MDSCs can improve antitumor immune response. Recent studies have demonstrated MDSCs can be suppressed by certain chemotherapeutic agents, such as 5-Fluorouracil (5-FU), gemcitabin and docetaxel. We hypothesized that treatment by 5-FU or surgical resection of primary tumors would prevent lung metastasis formation by inhibiting MDSCs. These results indicate that early-phase administration of 5-FU and early-phase resection of the primary tumor may provide therapeutic values to prevent MDSC-mediated lung metastases in tumor-bearing host. The results of our study may give a clue to develop a new strategy to control malignant tumors by regulating tumorassociated immune responses. Furthermore, we reviewed current research on the MDSC-targeted therapy.