Potentiation of Natural Killer Cells for Cancer Immunotherapy: A Review of Literature

Lowry, Lacy E.; Zehring, William A.

doi:10.3389/fimmu.2017.01061

Cited by 55 publications

(37 citation statements)

References 37 publications

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“…53,54 The increased abundance of NK cells is also an important finding as adoptive NK cell therapies are currently being explored and refined. 55,56 The potential of this therapeutic context will need to be experimentally validated as the presence of myeloid derived suppressor cells and M2 macrophages will present additional immunosuppressive hurdles. With the significant differences in lymphocyte abundance, activation status, and immune checkpoint expression between the metastatic and non-metastatic specimens, we expected to also observe significant variation in the TIS between the two sets of specimens.…”

Section: Discussionmentioning

confidence: 99%

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Sorenson

Hood

et al. 2019

OncoImmunology

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Osteosarcoma (OS) is the most common bone tumor in pediatric and adolescent/young adult patients yet little is known about the microenvironment that supports this aggressive disease. We have used targeted gene expression profiling and immunohistochemistry to characterize the microenvironment of metastatic and non-metastatic OS specimens from pediatric patients exhibiting poor histologic response to chemotherapy. Our results indicate that metastatic specimens exhibit lymphocyte exclusion as T cells are confined to the periphery of the pulmonary lesions. Furthermore, our data provides evidence of vascular dysfunction in metastatic OS indicated by increased expression of VEGFA, an increased ANGPT2: ANGPT1 gene expression ratio, and decreased expression of SELE, the gene encoding the adhesion molecule E-selectin. Moreover, correlation analyses show an inverse relationship between lymphocyte abundance and markers of vascular dysfunction exclusively in the metastatic specimens. Together, our data shows that the non-metastatic OS specimens demonstrate increased expression of various immunotherapeutic targets in comparison metastatic specimens and identifies vascular dysfunction and lymphocyte exclusion as important processes for therapeutic intervention in metastatic disease. ARTICLE HISTORY Results:Gene expression profiling of the tumor microenvironment and immuno-oncology landscape in pediatric OS Targeted gene expression profiling was performed on archived FFPE specimens from unmatched pediatric OS CONTACT Troy A. McEachron

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Section: Discussionmentioning

confidence: 99%

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Sorenson

Hood

et al. 2019

OncoImmunology

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“…In summary, our work has identified several critical components of a pathway exploited by Lm to elicit an immune-suppressive NK cell response. Although there are currently immunotherapy approaches focused on the improvement of NK cell responsiveness to tumors ( Lowry and Zehring, 2017 ), strategies to dampen NK cell anti-inflammatory responses remain unexplored. Our findings reveal several possible targets for interventions to limit NK cell IL-10 production during Lm and potentially other bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection

et al. 2018

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SUMMARYThe bacterial pathogen Listeria monocytogenes (Lm) capitalizes on natural killer (NK) cell production of regulatory interleukin (IL)-10 to establish severe systemic infections. Here, we identify regulators of this IL-10 secretion. We show that IL-18 signals to NK cells license their ability to produce IL-10. IL-18 acts independent of IL-12 and STAT4, which co-stimulate IFNγ secretion. Dendritic cell (DC) expression of Nlrp3 is required for IL-18 release in response to the Lm p60 virulence protein. Therefore, mice lacking Nlrp3, Il18, or Il18R fail to accumulate serum IL-10 and are highly resistant to systemic Lm infection. We further show that cells expressing or dependent on Batf3 are required for IL-18-inducing IL-10 production observed in infected mice. These findings explain how Il18 and Batf3 promote susceptibility to bacterial infection and demonstrate the ability of Lm to exploit NLRP3 for the promotion of regulatory NK cell activity.

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“…Natural killer cells. Natural killer (NK) cells are innate lymphoid cells that identify and kill tumor cells by sensing danger or damage signals (40). NK cells are found in GBM and have been shown to be effective at inducing lysis in GSCs (41).…”

Section: Immune Cellular Componentsmentioning

confidence: 99%

Brain Tumor Microenvironment and Host State: Implications for Immunotherapy

Tomaszewski

Sánchez-Pérez

Gajewski

et al. 2019

Clinical Cancer Research

251

197

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Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tumor cellextrinsic components that are native to the brain, as well as tumor-intrinsic mechanisms that aid in immune evasion. Lowering the barrier of immunosuppression by targeting the genetically stable tumor stroma presents opportunities to treat the tumor in a way that circumvents the complications of targeting a constantly mutating tumor with tumor antigen-directed therapies. Tumor-associated monocytes, macrophages, and microglia are a stromal element of particular interest. Macrophages and monocytes compose the bulk of infiltrating immune cells and are considered to have protumor and immunosuppressive effects. Targeting these cells or other stromal elements is expected to convert what is considered the "cold" TME of GBM to a more "hot" TME phenotype. This conversion could increase the effectiveness of what have become conventional frontline immunotherapies in GBM-creating opportunities for better treatment through combination therapy.

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Potentiation of Natural Killer Cells for Cancer Immunotherapy: A Review of Literature

Cited by 55 publications

References 37 publications

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection

Brain Tumor Microenvironment and Host State: Implications for Immunotherapy

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