Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer

Wang, Shuo; Qu, Yuan; Xia, Pengyan; Chen, Yi; Zhu, Xiaoxiao; Zhang, Jing; Wang, Guan; Tian, Yong; Ying, Jianming; Fan, Zusen

doi:10.1038/s41422-020-0312-y

Cited by 97 publications

(104 citation statements)

References 48 publications

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“…In another work, Wang et al identified six ILC subsets by performing single-cell RNA sequencing to profile tumor-infiltrating ILCs in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CRC) model [33]. Among those, three subsets expressed ILC2 signature genes (ILC2-A, -B, and -C).…”

Section: Pd-1 Expression On Ilcs In Cancermentioning

confidence: 99%

“…This shift was accompanied by an upregulation of TIGIT and CD96, and concomitant reduction in DNAM-1 levels, thus creating a pro-tumor environment [144]. Besides its effect on NK-ILC1 plasticity, TGF-β signaling was also reported to drive ILC3 conversion into ILCs with a regulatory phenotype [33]. Indeed, Wang et al [33] showed that during CRC progression, the proportion of ILC3s was decreased by concomitant expansion of Id3 + IL-10 secreting cells.…”

Section: Tigit and Cd96 And Tgf-βmentioning

confidence: 99%

“…Solid tumors, including Kaposi sarcoma, PC, ovarian and lung cancers [26][27][28][29][30], and HL [31] Use of anti-PD-1 or anti-PD-L1 improves the anti-tumor activity of NK cells against PD-L1/2+ tumor cells [25,26,31,32] ILC Decidual ILCs during pregnancy [17] Tumor-associated ILC2s (>PD-1 than circulating ILCs) [33] ILC2s and ILC3s in tumors of the gastrointestinal tract (>PD-1 than in the paralesional tissue) ILC3s in human malignant pleural effusion [30] ILC2s in colorectal cancer model [33] KIRs NK TIM-3 NK Gastric cancer [38] Lung adenocarcinoma [39] Advanced melanoma [40] Bladder cancer [38][39][40][41]…”

Section: Introductionmentioning

confidence: 99%

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Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

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Section: Pd-1 Expression On Ilcs In Cancermentioning

confidence: 99%

Section: Tigit and Cd96 And Tgf-βmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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“…TGFb is necessary for maintenance of ILCregs and autocrine TGFb is required for its expansion during intestinal inflammation. The role of ILCregs in colorectal cancer (CRC) show that these cells transdifferentiate from ILC3s during CRC progression via TGFb, indicating potential pro-tumorigenic function during ILC3-to-ILCreg plasticity (61). Furthermore, retinoic acid is reported to induce transdifferentiation of ILC2s into IL-10-producing ILCregs during airway inflammation (62), while ILC2s provide a predominant and inducible source of IL-10 in the GI tract (63).…”

Section: New Ilc On the Block: Ilcregsmentioning

confidence: 99%

Cytokine-Mediated Regulation of Innate Lymphoid Cell Plasticity in Gut Mucosal Immunity

2020

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Mucosal barriers are active sites that encounter a bombardment of antigenic stimuli derived from both the commensal flora and a variety of pathogens, as well as from environmental insults. As such, the ability to mount appropriate innate immune responses is an important first line of defense that confers protection to the host. Central to innate immunity are innate lymphoid cells (ILCs), which were first described a decade ago, and represent a family of heterogeneous cells driven by specific transcription factors and exhibit distinct cytokine profiles that are shared with their CD4+ T-helper cell counterparts. ILCs are particularly enriched at mucosal surfaces, and the tissue microenvironment and cytokine milieu in which ILCs reside are critical factors that drive the behavior and overall function of these cells. In fact, ILCs situated at mucosal barriers must be able to temper their response to a constant exposure of environmental antigens, but also promptly react to pathogens or signals that are potentially harmful to the host. In this context, the ability of ILCs to readily transdifferentiate in response to their dynamic surroundings has become a vigorous area of research, and defining specific mechanism(s) of ILC plasticity is at the advent of discovery. This review will summarize what is currently known regarding the network of cytokines and regulatory elements that enable ILCs to readily transform, based on the range of diverse signals and signal gradients they encounter that lead to either protective or pathogenic function(s), with focus on the gut mucosal immune system.

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“…In a recent paper published in Cell Research, Wang and colleagues, using azoxymethane/dextran sodium sulfate (AOM/ DSS) induced colorectal (CRC), profiled tumor-infiltrating ILCs in the early and late stages of cancer progression by single-cell RNA sequencing (scRNA-seq), flow cytometry and functional assays. 11 Collectively, six tumor-infiltrating ILC populations including ILC1, three ILC2 subsets (termed ILC2-A, B, C), ILC3 and ILCreg were identified. Wang et al demonstrated that ILC1s underwent changes consistent with impairment of their immune function.…”

mentioning

confidence: 99%