ILC2s: New Actors in Tumor Immunity

Ercolano, Giuseppe; Falquet, Maryline; Vanoni, Giulia; Trabanelli, Sara; Jandus, Camilla

doi:10.3389/fimmu.2019.02801

Cited by 36 publications

(31 citation statements)

References 116 publications

(117 reference statements)

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“…Two distinct subsets of ILC2 have been described: resident natural ILC2 and inflammatory ILC2, which can be induced upon IL-33 stimulation (81). High numbers of ILC2 can be found in many IL-33-enriched tumors, although their role in cancer immunity remains controversial (82). Ikutani et al first described an anti-tumoral role of ILC2 in a mouse model of melanoma.…”

Section: Il-33 As An Enhancer Of Anti-tumor Activities Of Ilc2mentioning

confidence: 99%

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

et al. 2020

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Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8+ T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.

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Section: Il-33 As An Enhancer Of Anti-tumor Activities Of Ilc2mentioning

confidence: 99%

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

et al. 2020

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“…While tumor-infiltrating NK cells are often associated with a good prognosis, the accumulation of ILC1s that have transdifferentiated from NK cells is correlated with a loss of anti-tumor protection 104 . Although immunosuppressive functions have been attributed to ILC2s found in tumors through their production of type 2 cytokines and enhancement of myeloid-derived suppressor cell function 105 , the role of these cells in tumor immunity is still fairly limited 106 . A recent study demonstrated that ILC2s could induce potent anti-tumor responses in pancreatic cancer and were associated with anti-PD-1 therapy efficacy 107 .…”

Section: Resident Innate Cells Are New Potent Drivers Of Tumor Protecmentioning

confidence: 99%

Tissue-resident lymphocytes: weaponized sentinels at barrier surfaces

et al. 2020

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Tissue-resident immune cells stably localize in tissues largely independent of the circulatory system. While initial studies have focused on the recognition of CD8+ tissue-resident memory T (CD8 TRM) cells, it is now clear that numerous cell types such as CD4+ T cells, gd T cells, innate lymphoid cells and mucosal-associated invariant T (MAIT) cells form stable populations in tissues. They are enriched at the barrier surfaces and within non-lymphoid compartments. They provide an extensive immune network capable of sensing local perturbations of the body’s homeostasis. This positioning enables immune cells to positively influence immune protection against infection and cancer but paradoxically also augment autoimmunity, allergy and chronic inflammatory diseases. Here, we highlight the recent studies across multiple lymphoid immune cell types that have emerged on this research topic and extend our understanding of this important cellular network. In addition, we highlight the areas that remain gaps in our knowledge of the regulation of these cells and how a deeper understanding may result in new ways to ‘target’ these cells to influence disease outcome and treatments.

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“…Studies have shown that several immune cells modulate CRC response by infiltrating the CRC microenvironment [3,4]. Among these immune cells, type 2 innate lymphoid cells (ILC2s) are abundant in the gut to regulate the gut homeostasis [5,6]. However, the role and underlying mechanism by which ILC2 involves CRC development has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

ILC2-derived IL-9 inhibit s colorectal cancer progression by activating CD8+ T cells

Wan

Huang

et al. 2020

Preprint

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Background Type 2 innate lymphoid cells (ILC2s), characterized by secreting type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. Methods ILC2s were sorted from the spleen using microbeads combined with flow cytometry and tumor infiltrating CD8+ T cells were isolated from tumor tissue by microbeads. Flow cytometry and immunofluorescence were used to detect the percentage of ILC2s and CD8+ T cells in the spleen and CRC tissue. Effects of IL-9 and IL-9-stimulated CD8+ T cells on CT26 cells were measured by proliferation, apoptosis, and migration assays in vitro. GEPIA was used to detect the ILC2s chemokines in CRC tissue and adjacent normal tissue. Results We found that ILC2s were increased in CRC tissue compared with the adjacent normal tissue. In vitro experiments showed that IL-9 could activate CD8+ T cells to promote the death of CT26 cells. ILC2s were the main IL-9-secreting cells in CRC tissue as shown by flow cytometry analysis. In vivo experiments showed that neutralizing ILC2s promoted the tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. Conclusions Our results demonstrated that ILC2-derived IL-9 activated CD8+ T cells to promote anti-tumor effects in CRC.

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ILC2s: New Actors in Tumor Immunity

Cited by 36 publications

References 116 publications

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Tissue-resident lymphocytes: weaponized sentinels at barrier surfaces

ILC2-derived IL-9 inhibit s colorectal cancer progression by activating CD8+ T cells

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