ArticleJournal of Cancer2017
Differentiation by NK cells is a prerequisite for effective targeting of cancer stem cells/poorly differentiated tumors by chemopreventive and chemotherapeutic drugs.
Article in Journal of Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 74 citations in OpenAlex.
- Stem cell-directed targeted chemotherapy primes drug-resistant metastatic ovarian tumors for elimination by natural killer cells.Molecular therapy. Oncology · 2026Article
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- Supercharged NK cells: a unique population of NK cells capable of differentiating stem cells and lysis of MHC class I high differentiated tumors.Cell death & disease · 2025Article
- Article
- Supercharged NK cells, unlike primary activated NK cells, effectively target ovarian cancer cells irrespective of MHC-class I expression.BMJ oncology · 2025Article
- Osteoclast-expanded supercharged NK cells perform superior antitumour effector functions.BMJ oncology · 2025Article
- Development of a genome atlas for discriminating benign, preinvasive, and invasive lung nodules.MedComm · 2024Article
- Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.Vaccines · 2024Review
- Review
- Medication-related osteonecrosis of the jaw (MRONJ): a review of pathogenesis hypothesis and therapy strategies.Archives of toxicology · 2024Review
- Article
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.International journal of molecular sciences · 2023Review
- Stem cell-assisted enzyme/prodrug therapy makes drug-resistant ovarian cancer cells vulnerable to natural killer cells through upregulation of NKG2D ligands.Medical oncology (Northwood, London, England) · 2023Article
- Augmentation of IFN-γ by bone marrow derived immune cells in the presence of severe suppression of IFN-γ in gingivae induced by zoledronic acid and denosumab in Hu-BLT mice model of ONJ.Frontiers in endocrinology · 2023Article
- Characterizing hepatocellular carcinoma stem markers and their corresponding susceptibility to NK-cell based immunotherapy.Frontiers in immunology · 2023Article
- Sequential therapy with supercharged NK cells with either chemotherapy drug cisplatin or anti-PD-1 antibody decreases the tumor size and significantly enhances the NK function in Hu-BLT mice.Frontiers in immunology · 2023Article
- Article
- Inability of ovarian cancers to upregulate their MHC-class I surface expression marks their aggressiveness and increased susceptibility to NK cell-mediated cytotoxicity.Cancer immunology, immunotherapy : CII · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural Killer (NK) cells target oral, pancreatic, lung, breast, glioblastoma and melanoma stem-like/poorly differentiated tumors. Differentiation of the abovementioned tumors with supernatants from split-anergized NK cells decreases their susceptibility to NK cells, but increases their sensitivity to cisplatin (CDDP)-mediated cell death. Breast and melanoma tumor cells with CD44 knockdown display enhanced susceptibility to NK cell-mediated lysis, potentially due to decreased differentiation. We also demonstrate that sulindac, a non-steroidal anti-inflammatory drug and a chemopreventive agent, not only limits the growth of oral tumor cells, but also aids in cancer cell elimination by NK cells. Treatment of oral tumors with sulindac, but not adriamycin inversely modulates the expression and function of NFκB and JNK, resulting in a significant down-regulation of IL-6, and VEGF secretion by oral tumor cells. In addition, increased secretion of IL-6 and VEGF is blocked by sulindac during interaction of oral tumors with NK cells. Sulindac treatment prevents synergistic induction of VEGF secretion by the tumor cells after their co-culture with untreated NK cells since non-activated NK cells lack the ability to efficiently kill tumor cells. Moreover, sulindac is able to profoundly reduce VEGF secretion by tumor cells cultured with IL-2 activated NK cells, which are able to significantly lyse the tumor cells. Based on the data presented in this study, we propose the following combinatorial approach for the treatment of stem-like/ poorly differentiated tumors in cancer patients with metastatic disease. Stem-like/ poorly differentiated tumor cells may in part undergo lysis or differentiation after NK cell immunotherapy, followed by treatment of differentiated tumors with chemotherapy and chemopreventive agents to eliminate the bulk of the tumor. This dual approach should limit tumor growth and prevent metastasis.
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