Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies

Kansler, Emily R.; Dadi, Saïda; Krishna, Chirag; Nixon, Briana G.; Stamatiades, Efstathios G.; Liu, Ming; Kuo, Fengshen; Zhang, Jing; Zhang, Xian; Capistrano, Kristelle J.; Blum, Kyle A.; Weiss, Kate; Kedl, Ross M.; Cui, Guangwei; Ikuta, Koichi; Chan, Timothy A.; Leslie, Christina; Hakimi, A. Ari; Li, Ming O.

doi:10.1038/s41590-022-01213-2

Cited by 49 publications

(66 citation statements)

References 51 publications

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“…Moreover, deletion of IL-15 in CRC patients was associated with a higher risk of relapse and reduced disease-free survival (126). Besides NK cells, mouse and human helper ILC1s have also been shown to respond to IL-15 (20,67,(127)(128)(129). Other ILC populations may also get activated in response to IL-15 in early tumors as IL-15 has been shown to induce conversion of ILC3s into IFN-g-producing ILC1s and cytotoxic NK cells (114,130).…”

Section: Il-15mentioning

confidence: 99%

Innate lymphoid cells in early tumor development

et al. 2022

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Innate and adaptive immune cells monitor, recognize, and eliminate transformed cells. Innate lymphoid cells (ILCs) are innate counterparts of T cells that play a key role in many facets of the immune response and have a profound impact on disease states, including cancer. ILCs regulate immune responses by responding and integrating a wide range of signals within the local microenvironment. As primarily tissue-resident cells, ILCs are ideally suited to sense malignant transformation and initiate anti-tumor immunity. However, as ILCs have been associated with anti-tumor and pro-tumor activities in established tumors, they could potentially have dual functions during carcinogenesis by promoting or suppressing the malignant outgrowth of premalignant lesions. Here we discuss emerging evidence that shows that ILCs can impact early tumor development by regulating immune responses against transformed cells, as well as the environmental cues that potentially induce ILC activation in premalignant lesions.

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Section: Il-15mentioning

confidence: 99%

Innate lymphoid cells in early tumor development

et al. 2022

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“…Together with NK cells, innate lymphoid cells (ILCs) have been also found both in tumor biopsies of CRC patients and in mouse models of CRC, playing both pro- and anti-tumor activities [ 22 , 23 , 24 , 25 ]. Added complexity is provided by the identification of ILCs expressing perforin and granzymes able to kill target cells, as well as by evidence in mice showing that NK cells and cytotoxic ILC can limit cancer growth [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In this review, we provide an overview of the features of NK cells and the expanding spectrum of innate lymphocytes with cytotoxic functions.…”

Section: Introductionmentioning

confidence: 99%

NK Cells and Other Cytotoxic Innate Lymphocytes in Colorectal Cancer Progression and Metastasis

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et al. 2022

IJMS

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Colorectal cancer (CRC) is one of the most common malignancies and leading causes of cancer-related deaths worldwide. Despite its complex pathogenesis and progression, CRC represents a well-fitting example of how the immune contexture can dictate the disease outcome. The presence of cytotoxic lymphocytes, both CD8+ T cells and natural killer (NK) cells, represents a relevant prognostic factor in CRC and is associated with a better overall survival. Together with NK cells, other innate lymphocytes, namely, innate lymphoid cells (ILCs), have been found both in biopsies of CRC patients and in murine models of intestinal cancer, playing both pro- and anti-tumor activities. In particular, several type 1 innate lymphoid cells (ILC1) with cytotoxic functions have been recently described, and evidence in mice shows a role for both NK cells and ILC1 in controlling CRC metastasis. In this review, we provide an overview of the features of NK cells and the expanding spectrum of innate lymphocytes with cytotoxic functions. We also comment on both the described and the potential roles these innate lymphocytes can play during the progression of intestinal cancer leading to metastasis. Finally, we discuss recent advances in the molecular mechanisms underlying the functional regulation of cytotoxic innate lymphocytes in CRC.

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“…Recently, Li and colleagues provided in Nature immunology 1 a novel mechanism of immunosurveillance in epithelial tumors, in which cytotoxic innate lymphoid cells (ILCs) sense IL-15 secreted by the tumor itself.…”

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confidence: 99%

“…In addition, NK cells and ILC1s showed an increased expression of the IL-2/IL-15 receptor β chain and chRCC tumors from TCGA cohort exhibited increased expression of IL-15, which is capable of enhancing anti-tumor responses. 1 …”

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confidence: 99%

“…as it was shown for fibrosarcoma progression in a murine cancer model. 1 , 3 Here, a mechanism of tumor immunoevasion was demonstrated in which TGFβ-driven conversion of NK cells into ILC1s leads to a suppressed antitumor immune response and thus enhanced tumorigenesis. 4 Future studies are needed to unravel the heterogeneous functional programs and plasticity of tissue-resident ILC1s within different types of cancer.…”

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confidence: 99%

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