Natural Killer Cell Immunotherapy for Osteosarcoma

Tullius, Brian P.; Setty, Buhvana A; Lee, Dean A.

doi:10.1007/978-3-030-43032-0_12

Cited by 11 publications

(9 citation statements)

References 86 publications

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“…During osteosarcoma progression, macrophages in the TME are reprogrammed toward an M2-like phenotype, further promoting osteosarcoma growth (Kelleher and O'Sullivan, 2017). Clinical studies have shown that in osteosarcoma patients, the number of circulating NK cells in the peripheral blood is significantly reduced, suggesting that NK cells play an important role in the development of osteosarcoma (Tullius et al, 2020). In addition, ANGPTL2 secretion by tumor cells has been demonstrated to recruit neutrophils into the lungs, triggering osteosarcoma lung metastasis (Charan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Zhang

et al. 2021

Front. Mol. Biosci.

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BackgroundOsteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients.MethodsWe obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration.ResultsWe initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells.ConclusionThe autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Zhang

et al. 2021

Front. Mol. Biosci.

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“…In humans, there are several families of activating receptors, including CD126 (FcRγIIIa), natural cytotoxicity receptors (NCRs), NK Group 2 (NKG2) lectin-like receptors, DNAM-1, and 2B4; however, most of these have not been well-characterized in the dog ( 32 ). Activating receptors generally recognize proteins that are upregulated by cell stress or are of non-self-origin, whereas inhibitory receptors primarily bind MHC for self-recognition ( 33 ). Inhibitory receptors provide control for NK cell activity against healthy tissue.…”

Section: Nk Cell Biologymentioning

confidence: 99%

“…Inhibitory receptors provide control for NK cell activity against healthy tissue. The primary inhibitory receptors in human NK cells are killer-cell immunoglobulin-like receptors (KIRs) and NKG2A, both of which bind to HLA class I molecules, preventing NK cell-mediated lysis of cells with normal HLA expression ( 33 ). MHC class-I deficient targets have heightened sensitivity to NK cell killing.…”

Section: Nk Cell Biologymentioning

confidence: 99%

“…Further, the release of pro-inflammatory cytokines enhances the recruitment and maturation of adaptive immune responses ( 42 , 43 ). The mechanism by which NK cells induce apoptosis in osteosarcoma cells may depend on both the activation state of the NK cells and the death receptor and apoptotic pathways present and functional in the target cell ( 33 ). For example, in vitro , direct NK cell lysis of osteosarcoma cells is mediated via direct release of granzyme B ( 44 ); however, granule-independent mechanisms may be more relevant in vivo , as losing Fas and TRAIL may be simpler mechanisms of escape than redundant downstream death pathways ( 45 ).…”

Section: Mechanisms Of Nk Cell Killingmentioning

confidence: 99%

“…Degranulation of NK cells is mediated by the balance of activating and inhibitory receptors, which in turn is influenced by the expression of ligands on the tumor cell. This suggests that NK cells isolated, expanded, and activated using different techniques may differ as to which activating receptors are highly expressed and important for recognizing a particular tumor ( 33 ). For example, in one study IL-15 stimulated NK cells targeted osteosarcoma predominantly through DNAM1, whereas in another study IL-2 stimulated NK cells targeted osteosarcoma predominantly through NKG2D ( 44 , 46 ).…”

Section: Mechanisms Of Nk Cell Killingmentioning

confidence: 99%

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Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma

Kisseberth

Lee

2021

Front. Vet. Sci.

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Osteosarcoma is the most common primary bone tumor in both humans and dogs. It is a highly metastatic cancer and therapy has not improved significantly since the inclusion of adjuvant chemotherapy into disease treatment strategies. Osteosarcoma is an immunogenic tumor, and thus development of immunotherapies for its treatment, especially treatment of microscopic pulmonary metastases might improve outcomes. NK cells are lymphocytes of the innate immune system and can recognize a variety of stressed cells, including cancer cells, in the absence of major histocompatibility complex (MHC)-restricted receptor ligand interactions. NK cells have a role in controlling tumor progression and metastasis and are important mediators of different therapeutic interventions. The core hypothesis of adoptive natural killer (NK) cell therapy is there exists a natural defect in innate immunity (a combination of cancer-induced reduction in NK cell numbers and immunosuppressive mechanisms resulting in suppressed function) that can be restored by adoptive transfer of NK cells. Here, we review the rationale for adoptive NK cell immunotherapy, NK cell biology, TGFβ and the immunosuppressive microenvironment in osteosarcoma, manufacturing of ex vivo expanded NK cells for the dog and provide perspective on the present and future clinical applications of adoptive NK cell immunotherapy in spontaneous osteosarcoma and other cancers in the dog.

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Immunotherapy of Osteosarcoma

Sorteberg

Lilienthal

et al. 2023

Handbook of Cancer and Immunology

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Natural Killer Cell Immunotherapy for Osteosarcoma

Cited by 11 publications

References 86 publications

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma

Immunotherapy of Osteosarcoma

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