Tumor-Infiltrating Natural Killer Cells

Cózar, Beatriz; Greppi, Marco; Carpentier, Sabrina; Narni-Mancinelli, Émilie; Chiossone, Laura; Vivier, Éric

doi:10.1158/2159-8290.cd-20-0655

Cited by 238 publications

(164 citation statements)

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“…[46][47][48] Importantly, this does not rule out that either molecule can regulate/inhibit both NK and CD8 + T cells. For instance, it has been shown that PD-1 blockade can unleash NK cells, 9,49 as well as CD8 + T cells. 50 Our data and a recent study 51 suggest that in current checkpoint blockade therapies, the effect on NK cell function may have been overlooked.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that natural killer (NK) cells are an important cell type for controlling certain types of cancer growth. 7 , 8 NK cells can identify and kill cancer cells through multiple mechanisms, including degranulation and direct killing 9 and can recruit various other immune cell populations to the tumor microenvironment via the release of chemokines and cytokines. 10 Reduced NK cell function has been associated with a worse disease outcome 11 and in some patient cohorts, the degree of NK cell infiltration in tumor tissues was associated with better prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers

et al. 2021

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Checkpoint blockade therapy is effective against many cancers; however, new targets need to be identified to treat patients who do not respond to current treatment or demonstrate immune escape. Here, we showed that blocking the inhibitory receptor Killer cell lectin-like receptor G1 (KLRG1) enhances anti-tumor immunity mediated by NK cells and CD8 + T cells. We found that loss of KLRG1 signaling alone significantly decreased melanoma and breast cancer tumor growth in the lungs of mice. In addition, we demonstrated that KLRG1 blockade can synergize with PD-1 checkpoint therapy to increase the therapeutic efficacy compared to either treatment alone. This effect was even observed with tumors that do not respond to PD-1 checkpoint therapy. Double blockade therapy led to significantly decreased tumor size, increased frequency and activation of CD8 + T cells, and increased NK cell frequency and maturation in the tumor microenvironment. These findings demonstrate that KLRG1 is a novel checkpoint inhibitor target that affects NK and T cell anti-tumor immunity, both alone and in conjunction with established immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers

et al. 2021

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“…The increase in Th17 cells significantly improves patient survival ( Asadzadeh et al, 2017 ; Qian et al, 2017 ). Eosinophils promote immune response and there are more NK cells in the tumor, which can kill the tumor better ( Malmberg et al, 2017 ; Moreira and Heinzerling, 2017 ; Cozar et al, 2020 ). Class2 had a worse outcome, with higher lymphocytes, MDSCs infiltration, immune checkpoint genes expression.…”

Section: Discussionmentioning

confidence: 99%

Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma

Zhang

et al. 2021

Front. Cell Dev. Biol.

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The tumor microenvironment is an important factor for the immunotherapy of tumor patients. The sequenced transcriptome data can be used to describe the tumor microenvironment and various immune subtypes. We exploited published data on patients with uveal melanoma (UVM) to identify immune subtypes. Based on the immune-related gene sets of 80 patients with UVM in the TCGA database, we used consensus clustering to identify two immune subgroups. In the two immune subtypes, we analyzed clinical characteristics and immune infiltration. Class1 has low immune infiltration, contains memory B cells, Th2 cells, Th17 cells, eosinophils, natural killer cells, and has a better prognosis. Class2 has higher immune infiltration. CD8+ T cells, Th1 cells, MDSCs, and Dendritic cells are enriched in class2, which has strong cytolytic activity, high expression of immune checkpoint genes, and poor outcome. Moreover, we have developed and verified an immune characteristic model that can predict the prognosis of patients well. Through this model, we screened prostaglandin-endoperoxide synthase 2 (PTGS2) as the therapeutic target of UVM. Treatment of choroidal melanoma cell line (OCM1) cells with celecoxib (an inhibitor of PTGS2) effectively inhibits cell growth, proliferation, and promotes apoptosis. Our results show the immunological heterogeneity of UVM patients and also provide an ideal therapeutic target for the future treatment design of patients.

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“…Inhibitory receptors include C-type lectin receptors (CD94/NKG2A/B) and KIRs (KIR-2DL and KIR-3DL). MHC class I (MHC-I) molecules are present on most cells, and NK cell inhibitory receptors (KIRs and CD94/ NKG2A/B) can bind to them to prevent NK cell-mediated killing (13)(14)(15)(16)(17); however, when stressed cells downregulated MHC-I expression, NK cells are activated through "missing-self recognition" by losing their inhibitory signals. When cancer cells show elevated level of NK cell receptor, like NKG2D in response to stress, "self-induced" activation mechanism occur and leading the engagement of NK cells.…”

Section: Introductionmentioning

confidence: 99%

The Adverse Impact of Tumor Microenvironment on NK-Cell

Wei

2021

Front. Immunol.

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NK cells are considered an important component of innate immunity, which is the first line of defensing against tumors and viral infections in the absence of prior sensitization. NK cells express an array of germline-encoded receptors, which allow them to eliminate abnormal cells and were previously considered a homogenous population of innate lymphocytes, with limited phenotypic and functional diversity. Although their characteristics are related to their developmental origins, other factors, such as tumors and viral infections, can influence their phenotype. Here, we provide an overview of NK cells in the context of the tumor microenvironment, with a primary focus on their phenotypes, functions, and roles in tumor micro-environment. A comprehensive understanding of NK cells in the tumor microenvironment will provide a theoretical basis for the development of NK cell immunotherapy.

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Tumor-Infiltrating Natural Killer Cells

Cited by 238 publications

References 100 publications

Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers

Combination blockade of KLRG1 and PD-1 promotes immune control of local and disseminated cancers

Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma

The Adverse Impact of Tumor Microenvironment on NK-Cell

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