Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis

Domvri, Kalliopi; Petanidis, Savvas; Anestakis, Doxakis; Tsavlis, Drosos; Bai, Chong; Huang, Haidong; Freitag, Lutz; Hohenforst-Schmidt, Wolfgang; Porpodis, Κonstantinos; Katopodi, Theodora

doi:10.1016/j.clim.2020.108620

Cited by 26 publications

(19 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung cancer, the commonest of which is non-small cell lung cancer (NSCLC), has the highest incidence and mortality rate among various tumors worldwide ( 17 ). It has been demonstrated that the frequency of ILC2s increases in patients with lung cancer, which promotes lung metastases and mortality by inhibiting NK cell cytotoxic function and enhancing regulatory T cell (Treg) immunosuppressive manner ( 18 – 20 ). However, little is known about the PD-1 expression of ILC and the role of PD-1 in ILC2s in human lung cancer.…”

Section: Introductionmentioning

confidence: 99%

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer

et al. 2021

View full text Add to dashboard Cite

BackgroundThere is increasing evidence that group 2 innate lymphoid cells (ILC2s) play an essential role in allergy and parasitic infection. However, the role of ILC2s in human lung cancer remains unclear.MethodsILC2s from peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HDs) and non-small cell lung cancer (NSCLC) patients, and NSCLC tumor tissues were analyzed via multicolor flow cytometry. ILC2s or CD14+ cells were sorted by fluorescence-activated cell sorting. qPCR and flow cytometry were performed to assess the gene and protein expression of the indicated molecules. M1-like and M2-like macrophages were induced from CD14+ monocytes in vitro.ResultsILC2s were significantly more enriched in PBMCs and tumor tissues from NSCLC patients than in HDs. After screening for the main immune checkpoint molecules, we found that PD-1 was upregulated in ILC2s in NSCLC patients. Functionally, PD-1high ILC2s from tumor tissues expressed higher levels of IL-4 and IL-13 regarding both mRNA and protein levels than PD-1low ILC2s. Furthermore, PD-1high ILC2s robustly boosted M2-like macrophage polarization in vitro, by secreting IL-4 and IL-13, while neutralization of IL-4 and IL-13 by antibodies abrogated M2-like macrophage polarization.ConclusionILC2s are enriched in NSCLC patients and upregulate PD-1 expression. Upregulation of PD-1 facilitates the immunosuppressive function of ILC2s. PD-1high ILC2s enhance M2-like macrophage polarization by secreting IL-4 and IL-13. PD-1 acts as a positive regulator of the immunosuppressive function of ILC2s in human NSCLC.

show abstract

Section: Introductionmentioning

confidence: 99%

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“… 19 Alternatively, the mutual interaction between Treg cells and MDSCs may be also involved. 36 , 41 , 42 Furthermore, the contribution of each immunosuppressive cell type to CCL28-induced tumor progression remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

CCL28 Downregulation Attenuates Pancreatic Cancer Progression Through Tumor Cell-Intrinsic and -Extrinsic Mechanisms

Yan

Yuan

Gui

et al. 2021

Technol Cancer Res Treat

View full text Add to dashboard Cite

C-C motif chemokine ligand 28 (CCL28) has been reported to be pro-tumoral in several cancer types. However, the role of CCL28 in pancreatic ductal adenocarcinoma (PDAC) progression remains unclear. CCL28 mRNA expression in tumors from PDAC patients was found to be elevated as compared to normal pancreas. CCL28 expression was also negatively correlated with overall survival (OS) in pancreatic cancer patients. Our in vitro experiments showed that CCL28 knockdown impairs the proliferation of mouse pancreatic cancer cell line PAN02. Moreover, in both immunocompetent syngeneic mice and immunodeficient NOD-SCID mice, CCL28 deficiency significantly attenuated the growth of subcutaneous PAN02 tumors. In syngeneic mouse model, CCL28 downregulation remodeled the pancreatic tumor microenvironment by suppressing the infiltration of both regulatory T (Treg) cells, myeloid-derived suppressor cells, and activated pancreatic stellate cells, and upregulating the expression of lymphocyte cytotoxic proteins including perforin and granzyme B. In conclusion, our work demonstrates that CCL28 is a potential target for pancreatic cancer treatment and CCL28 blockade could inhibit tumor growth through both tumor-cell-intrinsic and extrinsic mechanisms.

show abstract

“…Treatment with IL-9 activated ILC2-dependent Tregs and effectively attenuated inflammation ( 68 ). In addition, Treg-dependent immunosuppression is correlated with ILC2 augmentation, and Tregs can induce tumor metabolic reprogramming via the STING/ILC2 axis ( 69 ). PD-1 is highly inducible in IL-33-activated ILC2s, PD-1 deficiency converts the ILC2 metabolic process into glycolysis, glutamine catabolism and methionine catabolism, enhances the activation and proliferation of ILC2s induced by IL-33, and regulates the production and survival of cytokines in aILC2s, including IL5, IL-13, IL-9 and CSF2 ( 70 ).…”

Section: Initiation Of the Ilc2 Response During Allergic Reactionsmentioning

confidence: 99%

The Role of Type 2 Innate Lymphoid Cells in Allergic Diseases

et al. 2021

View full text Add to dashboard Cite

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases.

show abstract

Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis

Cited by 26 publications

References 48 publications

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer

CCL28 Downregulation Attenuates Pancreatic Cancer Progression Through Tumor Cell-Intrinsic and -Extrinsic Mechanisms

The Role of Type 2 Innate Lymphoid Cells in Allergic Diseases

Contact Info

Product

Resources

About