NK cell-based tumor immunotherapy

Zhang, Hao; Yang, Li; Wang, Tingting; Li, Zhen

doi:10.1016/j.bioactmat.2023.08.001

Cited by 19 publications

(6 citation statements)

References 241 publications

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“…NK cells are important immune cells that mediate tumor immunosurveillance ( 119 ). The recognition and elimination of target cells by NK cells do not require prior exposure to pathogens, especially those infected with viruses and mutated tumor cells ( 120 ).…”

Section: The Biological Roles and Functions Of Different Immune Cells...mentioning

confidence: 99%

Recent advances in understanding the immune microenvironment in ovarian cancer

Chen,

Yang,

et al. 2024

Front. Immunol.

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The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.

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Section: The Biological Roles and Functions Of Different Immune Cells...mentioning

confidence: 99%

Recent advances in understanding the immune microenvironment in ovarian cancer

Chen,

Yang,

et al. 2024

Front. Immunol.

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“…Among various immune cells, tumor-infiltrating NK cells are associated with prognosis in various cancers, such as colorectal cancer (CRC) (Zhong et al, 2022) , lung cancer (Villegas et al, 2002) , and gastric cancer (Ishigami et al, 2000) . Recently, based on their anti-tumor potential, NK cells were exploited for treating malignancies and have proven to be highly promising for the treatment of certain hematologic malignancies (Lamb et al, 2021, Liu et al, 2020) but have limited efficacy for treating solid tumors (Zhang et al, 2024, Hu et al, 2019, Oh et al, 2019) . Additionally, intratumor NK cells differ phenotypically or functionally from peripheral NK cells in several malignancies (Bruno et al, 2013, Carrega et al, 2008) ; a specific subset of tumor-infiltrating NK cells (CD11b − and CD27 − ) was associated with tumor progression in lung and hepatocellular cancers (Zhang et al, 2017, Jin et al, 2013) .…”

Section: Introductionmentioning

confidence: 99%

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

Mao,

Chen,

xing

et al. 2024

Preprint

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Purpose: The abundance and biological contribution of Natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Methods: We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA-sequencing datasets to investigate NK cells' biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Results: We used single-cell RNA sequencing and spatial transcriptomics to map the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a resting status, as evidenced by decreased KIR2DL4 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation and release of SCF on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. Conclusion: Together, our findings revealed a population of protumorigenic NK cells that may be exploited for novel therapeutic strategies to improve therapeutic outcomes for patients with CCLM.

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“…NK cells have intrinsic antitumor capabilities, which are controlled by a wide range of activating/costimulatory and inhibitory receptors. Due to these properties, NK cells represent an attractive agent for cancer cell therapy [ 1 ]. Although NK cells are capable of recognizing and killing without prior sensitization, their functional activity can be significantly increased during activation, which is essential for NK-cell-based adoptive immunotherapy [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells

Alekseeva,

Streltsova,

Vavilova

et al. 2024

Pharmaceutics

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Human cytomegalovirus (HCMV)-specific adaptive NK cells are capable of recognizing viral peptides presented by HLA-E on infected cells via the NKG2C receptor. Using retroviral transduction, we have generated a K562-cell-based line expressing HLA-E in the presence of the HLA-E-stabilizing peptide, which has previously shown the capacity to enhance adaptive NK cell response. The obtained K562-21E cell line was employed to investigate proliferative responses of the CD57− NK cell subset of HCMV-seropositive and seronegative donors. Stimulation of CD57− NK cells with K562-21E/peptide resulted in an increased cell expansion during the 12-day culturing period, regardless of the serological HCMV status of the donor. The enhanced proliferation in response to the peptide was associated with a greater proportion of CD56brightHLA-DR+ NK cells. In later stages of cultivation, the greatest proliferative response to K562-21E/peptide was shown for a highly HCMV-seropositive donor. These expanded NK cells were characterized by the accumulation of CD57−KIR2DL2/3+NKG2C+NKG2A− cells, which are hypothesized to represent adaptive NK cell progenitors. The K562-21E feeder cells can be applied both for the accumulation of NK cells as therapeutic effectors, and for the study of NK cell maturation into the adaptive state after the HLA-E peptide presentation.

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NK cell-based tumor immunotherapy

Cited by 19 publications

References 241 publications

Recent advances in understanding the immune microenvironment in ovarian cancer

Recent advances in understanding the immune microenvironment in ovarian cancer

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells

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