"The functional in vitro and in vivo immunogenicity of CSCs has been deliberated in a limited number of cases. Interestingly, a new group of molecules, the heat-shock proteins (HSP), commonly expressed in many murine and human tumors and to be immunogenic in vivo and in vitro (Parmiani et al. 2007), have been demonstrated to preserve CSCs or at least for a subfamily of them (HSP40). These HSPs demonstrated high expression in most human solid tumors including renal cell carcinoma (RCC), and prompted cytotoxic T lymphocytes (CTL) reactions in vitro favored with a therapeutic potential at least in the mouse system (Nishizawa et al. 2012). "
[Show abstract][Hide abstract] ABSTRACT: Cancer stem cells (CSCs) need to survive cancer treatments with a specific end goal to provide new, more differentiated, metastatic-prone cancerous cells. This happens through diverse signals delivered within the tumor microenvironment where ample evidence indicates that altered developmental signaling pathways play an essential role in maintaining CSCs and accordingly the survival and the progression of the tumor itself. This review summarizes findings on the immunobiological properties of CSCs as compared with cancerous non-stem cells involving the expression of immunological molecules, cytokines and tumor antigens as well as the roles of the Notch, Wnt and Hedgehog pathways in the brain, breast and colon CSCs. We concluded that if CSCs are the main driving force behind tumor support and growth then understanding the molecular mechanisms and the immunological properties directing these cells for immune tolerance is of great clinical significance. Such knowledge will contribute to designing better targeted therapies that could prevent tumor recurrence and accordingly significantly improve cancer treatments and patient survival.
"Besides this apparent solution for the selection of antigens for cancer vaccines, universal TAA have several drawbacks that obviate this hypothesis. For instance, it remains to be established whether they are more immunogenic when compared with other TAA obtained from the same tumor . Also, the frequency of peptide-specific CTL precursors in peripheral blood mononuclear cells (PBMC), which is determinant for the generation of the final number of effector T cells, can be very low and not overcome tumor escape from immune surveillance . "
[Show abstract][Hide abstract] ABSTRACT: The concept of therapeutic cancer vaccines is based on the activation of the immune system against tumor cells after the presentation of tumor antigens. Nanoparticles (NPs) have shown great potential as delivery systems for cancer vaccines as they potentiate the co-delivery of tumor-associated antigens and adjuvants to dendritic cells (DCs), insuring effective activation of the immune system against tumor cells. In this review, the immunological mechanisms behind cancer vaccines, including the role of DCs in the stimulation of T lymphocytes and the use of Toll-like receptor (TLR) ligands as adjuvants will be discussed. An overview of each of the three essential components of a therapeutic cancer vaccine - antigen, adjuvant and delivery system - will be provided with special emphasis on the potential of particulate delivery systems for cancer vaccines, in particular those made of biodegradable aliphatic polyesters, such as poly(lactic-co-glycolic acid) (PLGA) and poly-ε-caprolactone (PCL). Some of the factors that can influence NP uptake by DCs, including size, surface charge, surface functionalization and route of administration, will also be considered.
"This is made more difficult by the role that epigenetic regulation plays in cancer stem cells. Additionally, targeting universal TAAs such as human telomerase reverse transcriptase and inhibitor of apoptosis proteins might be important for effectively targeting tumours with immunotherapy, as will combining these treatments with ones that target unique stem-ness-related antigens . Several additional markers and signalling molecules, such as the Hh/Patched pathway, as well as the ABCG2 drug transporters could be used as potential targets of therapy for breast cancer . "
[Show abstract][Hide abstract] ABSTRACT: The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to more meaningful clinical remissions. Here, we review the role of stem cells in the healthy breast, the role of breast cancer stem cells in disease, and the potential to target these cells.
Breast cancer research: BCR 08/2008; 10(4):210. DOI:10.1186/bcr2111 · 5.88 Impact Factor
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