B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer

Zhu, Zheng; Teng, Kun-Yu; Zhou, Jian; Xu, Yunyun; Zhang, Lifeng; Zhao, Hua; Zhang, Xueguang; Tian, Lei; Li, Zhiyao; Lu, Ting; Ma, Shoubao; Dai, Zhenyu; Wang, Jing; Chen, Xingyu; Wu, Xing; Pan, Yihan; Shi, Wenyu; You, Zhiqun; Chen, Hanyu; Chung, Vincent; Yu, Jianhua; He, Songbing; Zhao, Xin; Cao, Lei; Li, Dechun

doi:10.3389/fonc.2022.814312

Cited by 5 publications

(4 citation statements)

References 45 publications

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Section: Discussionmentioning

confidence: 99%

“…There is a lack of consensus on the links between NKR ligand expression and prognosis in a host of cancers [ 61 , 62 , 63 , 64 , 65 ]. In ovarian, head and neck, and pancreatic cancers, the expression of NKR ligands B7-H6, ULBP2, RAET1E, and death receptor TRAIL-R were associated with a poorer prognosis [ 61 , 63 , 64 ]. However, in the setting of colorectal and breast cancers, high NKR ligand MICA/B and ULBP2 expression was associated with a better prognosis for patients [ 62 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses

et al. 2023

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Glioblastoma multiforme (GBM) is the most common adult primary brain malignancy, with dismal survival rates of ~14.6 months. The current standard-of-care consists of surgical resection and chemoradiotherapy, however the treatment response is limited by factors such as tumour heterogeneity, treatment resistance, the blood–brain barrier, and immunosuppression. Several immunotherapies have undergone clinical development for GBM but demonstrated inadequate efficacy, yet future combinatorial approaches are likely to hold more promise. Olaparib is FDA-approved for BRCA-mutated advanced ovarian and breast cancer, and clinical studies have revealed its utility as a safe and efficacious radio- and chemo-sensitiser in GBM. The ability of Olaparib to enhance natural killer (NK) cell-mediated responses has been reported in prostate, breast, and lung cancer. This study examined its potential combination with NK cell therapies in GBM by firstly investigating the susceptibility of the GBM cell line T98G to NK cells and, secondly, examining whether Olaparib can sensitise T98G cells to NK cell-mediated responses. Here, we characterise the NK receptor ligand profile of T98G cells and demonstrate that Olaparib does not dampen T98G susceptibility to NK cells or elicit immunomodulatory effects on the function of NK cells. This study provides novel insights into the potential combination of Olaparib with NK cell therapies for GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses

et al. 2023

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“…In patients with pancreatic cancer, the B7-H6 expression on tissues has been associated with tumor progression and metastasis while notably the soluble form of it has shown the same profile in these patients. 159 Shorter OS was seen also at high expressed levels of both the B7-H6 cell surface and sB7-H6. In this study, the in vitro knocking out of B7-H6-induced NK cells increased cytokine production and increased the PC tumor cells’ interaction with NK-mediated cytotoxicity.…”

Section: New B7 Family Checkpoints Moleculesmentioning

confidence: 97%

Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands

Kamali,

Bautista,

Eisenhut

et al. 2023

Therapeutic Advances in Vaccines and Immunotherapy

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Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses.

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“…B7-H6 is a B7 costimulatory family member that is overexpressed and associated with poorer outcomes in cancer ( 201 , 202 ). B7-H6 and BAT-3 can be shed from the membrane and antagonize NCR binding to prevent NK cell activation ( 203 ).…”

Section: Receptor Driven Signaling In Natural Killer Cellsmentioning

confidence: 99%

Killer instincts: natural killer cells as multifactorial cancer immunotherapy

Nersesian,

Carter,

Lee

et al. 2023

Front. Immunol.

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Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.

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B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer

Cited by 5 publications

References 45 publications

Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses

Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses

Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands

Killer instincts: natural killer cells as multifactorial cancer immunotherapy

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