Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells

Ferreira-Teixeira, Margarida; Parada, B.; Paiva-Oliveira, Daniela I.; Alves, Vera; Sousa, Vítor; Chijioke, Obinna; Münz, Christian; Reis, Flávio; Rodrigues-Santos, Paulo

doi:10.1016/s1569-9056(17)31016-3

Cited by 15 publications

(31 citation statements)

References 26 publications

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“…A similar preference for CSCs by NK cells was revealed in colon cancer, melanoma, and glioblastoma . In bladder cancer, chemoresistant CSCs treated with activated‐NK cell supernatants demonstrated decreased stemness (as measured by ALDH activity and mRNA panel for stem markers) and increased cisplatin sensitivity . Together, these findings reveal that NK cells can target and kill CSCs if they are able to penetrate the tumor and overcome the tumor's defense mechanisms.…”

Section: Immune Modulationsupporting

confidence: 55%

Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells

Relation¹,

Dominici

Horwitz

2017

Stem Cells

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Cancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules. The TME acts as a therapeutic barrier through immunosuppressive, and thereby tumor-promoting, actions. These factors, outside of the cancer cell lineage, work in concert to shelter CSCs from both the body's intrinsic anticancer immunity and pharmaceutical interventions to maintain cancer growth. Emerging therapies aimed at the TME offer a promising new tool in breaking through this shield to target the CSCs, yet definitive treatments remain unrealized. In this review, we summarize the mechanisms by which CSCs are protected by the TME and current efforts to overcome these barriers. STEM CELLS 2017;35:1123-1130 SIGNIFICANCE STATEMENTCancer stem cells differ from bulk tumor cells due to their ability to create a heterogeneous tumor population, unlimited self-renewal, and proliferation. The tumor microenvironment (TME) provides a shelter for these cells through the presence and actions of stroma, vasculature, extracellular matrix, signaling molecules, and immune cells. The TME has increasingly been recognized as an important component of therapy resistance and tumor progression. Unlike tumor cells, the critical components that comprise the TME and their roles in tumor progression are common between different cancers. A thorough understanding of cancer stem cell-TME interactions is vital to the development of innovative therapeutics.

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Section: Immune Modulationsupporting

confidence: 55%

Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells

Relation¹,

Dominici

Horwitz

2017

Stem Cells

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“…This combination strategy could be applied clinically as a way to reduce patient relapse rates and improve the utility of both NK-cell transfer and radiotherapy (Figure 1). NK cells have also been future science group Leveraging natural killer cells for cancer immunotherapy Review found to synergize with chemotherapy to target CSCs in preclinical models of nonmuscle invasive bladder cancer [66]. While the role of the cancer stem cell populations in human cancer progression remains controversial, the ability of NK cells to target cancer stem cells may offer a paradigm shift in cancer treatment approaches.…”

Section: Adoptive Nk-cell Therapymentioning

confidence: 99%

Leveraging Natural Killer Cells for Cancer Immunotherapy

2017

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Natural killer (NK) cells are potent antitumor effector cells of the innate immune system. Based on their ability to eradicate tumors in vitro and in animal models, significant enthusiasm surrounds the prospect of leveraging human NK cells as vehicles for cancer immunotherapy. While interest in manipulating the effector functions of NK cells has existed for over 30 years, there is renewed optimism for this approach today. Although T cells receive much of the clinical and preclinical attention when it comes to cancer immunotherapy, new strategies are utilizing adoptive NK-cell immunotherapy and monoclonal antibodies and engineered molecules which have been developed to specifically activate NK cells against tumors. Despite the numerous challenges associated with the preclinical and clinical development of NK cell-based therapies for cancer, NK cells possess many unique immunological properties and hold the potential to provide an effective means for cancer immunotherapy.

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“…124 On the other hand, adoptive transfer of NK cells can eliminate the cancer stem cell compartment making the tumour more differentiated and sensitive to chemotherapeutic drugs. 125,126 With regards to innovative therapies, proteasome inhibition, which reduces MHC class I molecules expression, have been shown to upregulate MICA/B and death receptors on several solid tumour CSCs, enhancing NK cell-mediated killing and tumour regression in vivo after NK cell adoptive transfer. 127 Another field of active research is the development of mAbs specifically targeting CSC surface markers.…”

Section: And Solid Tumor Derived Cancer Stem Cellsmentioning

confidence: 99%

“…For instance, radiotherapy, in addition to eliminating tumour bulk, has been shown to induce the upregulation of NK cell‐activating ligands on surviving CSCs, enhancing NK cells cytotoxicity and improving survival when NK cells are infused in the host . On the other hand, adoptive transfer of NK cells can eliminate the cancer stem cell compartment making the tumour more differentiated and sensitive to chemotherapeutic drugs …”

Section: Natural Killer Cells and Solid Tumor Derived Cancer Stem Cellsmentioning

confidence: 99%

New avenues for melanoma immunotherapy: Natural Killer cells?

et al. 2020

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Human solid malignant tumours may be particularly resistant to conventional therapies. Among solid tumours, immunological features of cutaneous melanoma have been well characterized in the past and today melanoma patients are routinely treated with the anti‐immune checkpoints immunotherapy that has completely changed metastatic melanoma treatment and prognosis. Two cytotoxic cell populations may lead to the physical elimination of tumour cell targets: cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Tumour recognition by CTLs depends on major histocompatibility complex (MHC) class I molecules, while NK cells recognize tumours expressing low or null levels of MHC class I molecules. Despite this well‐established complementarity, NK cells are still left behind in the optimization of innovative immunotherapy approaches. NK cells are members of innate lymphoid cells (ILCs) that play a critical role in early host defence against invading pathogens and transformed cells. Recent findings suggest that NK cell frequencies directly correlate with the overall survival of ipilimumab‐treated melanoma patients. Furthermore, in vitro and in vivo evidences indicate that NK cells can selectively kill cancer stem cells, reducing tumour size and delaying metastatic progression. The aim of this review is to provide a survey of the evidences indicating NK cells as an excellent candidate to complement the newest solid tumour immunotherapy approaches.

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Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells

Cited by 15 publications

References 26 publications

Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells

Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells

Leveraging Natural Killer Cells for Cancer Immunotherapy

New avenues for melanoma immunotherapy: Natural Killer cells?

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