Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy

Peng, Peng; Lou, Yue; Wang, Shicheng; Wang, Junjun; Zhang, Zelu; Du, Peishan; Liu, Ping; Xu, Lisa X.

doi:10.1136/jitc-2022-005769

Cited by 16 publications

(17 citation statements)

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“…In addition, it has been shown that the interaction of NK cells with myeloid-derived suppressor cells (MDSCs) is involved in indirect mechanisms of T cell-NK cell crosstalk. Activated NK cells after cryo-thermal therapy reduced MDSCs accumulation via NKG2D-NKG2D ligands axis and reprogrammed MDSCs to a mature phenotype via IFN-γ, promoting CD4 Th1-dominant antitumour immunity in the B16F10 melanoma model [ 48 ]. Notably, evidence of bidirectional crosstalk between NK cells and T cells has emerged.…”

Section: Crosstalk Between Nk Cells and The Tmementioning

confidence: 99%

NK cells are never alone: crosstalk and communication in tumour microenvironments

Zhou

Lu²,

Liu

et al. 2023

Mol Cancer

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Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.

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Section: Crosstalk Between Nk Cells and The Tmementioning

confidence: 99%

NK cells are never alone: crosstalk and communication in tumour microenvironments

Zhou

Lu²,

Liu

et al. 2023

Mol Cancer

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“…In recent years, NK cells are increasingly considered important for immunotherapy [ 11 , 65 ], impelling us to explore their role in predicting the immunotherapeutic response of ovarian cancer patients. Interactions between T cells and NK cells were widely reported [ 66 , 67 , 68 , 69 ], and two genes forming the prognostic risk model were found to participate in the regulating function of both T cells and NK cells, namely SLC11A1 [ 46 , 70 , 71 , 72 ] and EVL [ 51 , 73 , 74 , 75 ]. Thus, we infer that immunotherapeutic response might also be predicted by evaluating the functional state of NK cells.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prognostic Risk Model Based on Nature Killer Cells for Serous Ovarian Cancer

Zhang

Qin

Lin

2023

JPM

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Nature killer (NK) cells are increasingly considered important in tumor microenvironment, but their role in predicting the prognosis of ovarian cancer has not been revealed. This study aimed to develop a prognostic risk model for ovarian cancer based on NK cells. Firstly, differentially expressed genes (DEGs) of NK cells were found by single-cell RNA-sequencing dataset analysis. Based on six NK-cell DEGs identified by univariable, Lasso and multivariable Cox regression analyses, a prognostic risk model for serous ovarian cancer was developed in the TCGA cohort. This model was then validated in three external cohorts, and evaluated as an independent prognostic factor by multivariable Cox regression analysis together with clinical characteristics. With the investigation of the underlying mechanism, a relation between a higher risk score of this model and more immune activities in tumor microenvironment was revealed. Furthermore, a detailed inspection of infiltrated immunocytes indicated that not only quantity, but also the functional state of these immunocytes might affect prognostic risk. Additionally, the potential of this model to predict immunotherapeutic response was exhibited by evaluating the functional state of cytotoxic T lymphocytes. To conclude, this study introduced a novel prognostic risk model based on NK-cell DEGs, which might provide assistance for the personalized management of serous ovarian cancer patients.

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“…A recent study demonstrated that the predominance and persistence of CD4 + T cells could induce decade-long leukemia remission ( 34 ). Therefore, stimulating CD4 + T cells is crucial to achieving long-term antitumor immune memory in cancer immunotherapy ( 35 ). In this research, CD4 + memory T cells take up high contents in the tumor environment.…”

Section: Discussionmentioning

confidence: 99%

Predicting prognosis and clinical efficacy of immune checkpoint blockade therapy via interferon-alpha response in muscle-invasive bladder cancer

Fan¹,

Zheng²,

Wang³

et al. 2023

Pathol. Oncol. Res.

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Background: Immune checkpoint blockade (ICB) can prompt durable and robust responses in multiple cancers, involving muscle-invasive bladder cancer (MIBC). However, only a limited fraction of patients received clinical benefit. Clarifying the determinants of response and exploring corresponding predictive biomarkers is key to improving outcomes.Methods: Four independent formerly published cohorts consisting of 641 MIBC patients were enrolled in this study. We first analyzed the associations between various cancer hallmarks and ICB therapy response in two immunotherapeutic cohorts to identify the leading prognostic hallmark in MIBC. Furthermore, advanced machine learning methods were performed to select robust and promising predictors from genes functioning in the above leading pathway. The predictive ability of selected genes was also validated in multiple MIBC cohorts.Results: We identified and verified IFNα response as the leading cancer hallmark indicating better treatment responses, favorable overall survival, and an inflamed tumor microenvironment with higher infiltration of immune effector cells in MIBC patients treated with ICB therapy. Subsequently, two commonly selected genes, CXCL10 and LAMP3, implied better therapy response and the CXCL10highLAMP3high patients would benefit more from ICB therapy, which was comprehensively validated from the perspective of gene expression, clinical response, patient survival and immune features.Conclusion: Higher IFNα response primarily predicted better ICB therapeutic responses and reflected an inflamed microenvironment in MIBC. A composite of CXCL10 and LAMP3 expression could serve as promising predictive biomarkers for ICB therapeutic responses and be beneficial for clinical decision-making in MIBC.

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Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy

Cited by 16 publications

References 50 publications

NK cells are never alone: crosstalk and communication in tumour microenvironments

NK cells are never alone: crosstalk and communication in tumour microenvironments

Development and Validation of a Prognostic Risk Model Based on Nature Killer Cells for Serous Ovarian Cancer

Predicting prognosis and clinical efficacy of immune checkpoint blockade therapy via interferon-alpha response in muscle-invasive bladder cancer

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