Immunotherapeutic Strategies to Target Cancer Stem Cells: State of the Art in Basic Research to Clinical Application

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Background

Cancer stem cells (CSCs) are a subpopulation of tumor-forming cells capable of self-renewal, differentiation, and quiescence. Many neoplastic and invasive characteristics of malignant tumors, such as immune escape, angiogenesis, multidrug resistance, and recurrence after therapies, are attributed to CSCs. Over the years, tremendous advances have been made in characterizing and combating CSCs to increase the efficacy of anti-tumor therapeutic approaches and improve patients' survival rates. Despite numerous disappointing efforts and unequivocal clinical failures to target CSCs, the field of cancer immunotherapy has recently received significant attention.

Cancer immunotherapy is described as recruiting various patients' immune system arms to eliminate primary tumors, suppress secondary metastasis, and prevent recurrence after treatments. The field of cancer immunotherapy was revitalized after impressive successful experiences with introducing ipilimumab as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibodies and nivolumab as anti-programmed cell death protein 1 (PD1) antibodies for the treatment of melanoma in 2011 and 2015. In this regard, multiple immunotherapeutic approaches have been studied, from immunizing patients against tumoral antigens to applying oncolytic viruses to destroy cancer cells. These approaches are categorized as vaccines, adoptive cell therapy, oncolytic virus therapy, and immune checkpoint blockade.

Targeting CSCs exploiting immunotherapeutic approaches can be a game-changer prospect in the field of cancer treatment. Considering the concept of cancer stem cell plasticity, described as the capacity to dynamically switch between CSC and non-CSC states, targeting the population of CSCs along with non-CSCs in tumors is necessary to optimize therapeutic outcomes. Up to now, several studies have characterized CSC biomarkers in order to diagnose and predict survival rates. However, cancer immunotherapeutic approaches would be more personalized, targeted, and efficient by using CSC biomarkers. Now the era of cancer immunotherapy is at a breath taking pace regarding exploring new therapeutic targets which destroy tumors and their trace. From previous experience on identifying novel CSC markers in various solid tumors, CAR T-cells, CSC-based vaccines (therapeutics and preventive), exosomes derived from cancer stem cell-enriched spheroids (CSCenr-EXOs), producing monoclonal antibody against CSC antigens and tumor microenvironment. In this way, we are encouraged to propose a research topic that focuses on novel strategies to improve the efficiency of cancer immunotherapies, comprehensively understand possible targets in cancer stem cells, suggest novel approaches to eliminate tumors, and finally translate them to clinical practice to improve the life quality of patients.

We welcome different article types, including Original Research, Brief Research Report, Case Report, Classification, Clinical Trial, General Commentary, Hypothesis & Theory, Methods, Mini Review, Opinion, Perspective, Review, Systematic Review, Technology and Code that focus on, but are not limited to, the following sub-topics:
• Characterizing new CSC biomarkers for immune targeting approaches
• Identifying predictive biomarkers of immune checkpoint therapy
• Chimeric antigen receptor (CAR) T-cells in CSC immunotherapy
• The possible role of epigenetic mechanisms in targeting CSCs
• Signaling pathways involved in CSC-based immunotherapy
• Targeting the metabolic pathways involved in the maintenance of the CSCs (targeting metabolism in CSCs)
• Evaluating CSCs' quiescence for immune targeting approaches
• New pharmacological agents to target CSCs
• Crosstalk among tumor microenvironmental (TME), immune cells, and CSCs (targeting the TME)
• Targeting CSCs using vaccine Nanodiscs (nanovaccine)
• Identifying extracellular vesicles of CSCs, including exosomes for immune targeting approaches
• Clinical trials of immunotherapy in cancers

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.

Keywords: Immunotherapy, Cancer stem cells, Tumor, Targeted therapy, Vaccines, CAR T-cells, Biomarker

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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