CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy

Liu, Jinqing; Hu, Aiyan; Zhu, Jie; Yu, Jianyu; Talebian, Fatemeh; Bai, Xue‐Feng

doi:10.1007/978-3-030-35582-1_8

Cited by 46 publications

(43 citation statements)

References 59 publications

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“…6a ). DC_C3_LAMP3 cells were also predicted to interact with CD8_C11_PDCD1 cells through CD200-CD200R signalling, a non-classical immune-suppressive pathway involved in the suppression of anti-tumour responses 37 (Fig. 6b ).…”

Section: Resultsmentioning

confidence: 99%

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

et al. 2021

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The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

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Section: Resultsmentioning

confidence: 99%

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

et al. 2021

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“…CD200 receptor (CD200R) is an immunoregulatory receptor prominently expressed in the lungs, and mainly reported among alveolar macrophages, neutrophils, mast cells 9 – 11 . Previous studies have shown CD200-deficient mice have increased pulmonary alveolar macrophage activity in a mouse influenza model, which leads to increased mortality and hindered resolution of pulmonary inflammation 9 .…”

Section: Introductionmentioning

confidence: 99%

CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

et al. 2021

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The prevalence of asthma and airway hyperreactivity (AHR) is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) are copious producers of type 2 cytokines, which leads to AHR and lung inflammation. Here, we show that mouse ILC2s express CD200 receptor (CD200R) and this expression is inducible. CD200R engagement inhibits activation, proliferation and type 2 cytokine production, indicating an immunoregulatory function for the CD200–CD200R axis on ILC2s. Furthermore, CD200R engagement inhibits both canonical and non-canonical NF-κB signaling pathways in activated ILC2s. Additionally, we demonstrate both preventative and therapeutic approaches utilizing CD200R engagement on ILC2s, which lead to improved airway resistance, dynamic compliance and eosinophilia. These results show CD200R is expressed on human ILC2s, and its engagement ameliorates AHR in humanized mouse models, emphasizing the translational applications for treatment of ILC2-related diseases such as allergic asthma.

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“…It interacts with the transmembrane glycoprotein CD200, which can be expressed on a variety of cells, including CD4 + and CD8 + T cells and tumor cells. CD200/CD200R signaling has been linked to the regulation of macrophage activation and appears to inhibit T cell responses [ 42 ]. CD200R1 was highly upregulated on TAMs compared to macrophages from normal lung (LFC = 4.0, p < 0.0001) and, to a lesser degree, on CD8 + T cells (LFC = 1.65, p .adj = 0.01).…”

Section: Resultsmentioning

confidence: 99%

Analysis of Intra-Tumoral Macrophages and T Cells in Non-Small Cell Lung Cancer (NSCLC) Indicates a Role for Immune Checkpoint and CD200-CD200R Interactions

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Subbannayya

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et al. 2021

Cancers

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Non-small cell lung carcinoma (NSCLC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths. Immunotherapy with immune checkpoint inhibitors shows beneficial responses, but only in a proportion of patients. To improve immunotherapy in NSCLC, we need to map the immune checkpoints that contribute immunosuppression in NSCLC-associated immune cells and to identify novel pathways that regulate immunosuppression. Here, we investigated the gene expression profiles of intra-tumoral immune cells isolated from NSCLC patients and compared them to the expression profiles of their counterparts in adjacent healthy tissue. Transcriptome analysis was performed on macrophages, CD4+ and CD8+ T cells. The data was subjected to Gene Ontology (GO) term enrichment and weighted correlation network analysis in order to identify mediators of immunosuppression in the tumor microenvironment in NSCLC. Immune cells from NSCLC revealed a consistent differential expression of genes involved in interactions between myeloid cells and lymphocytes. We further identified several immunosuppressive molecules and pathways that may be activated in tumor-associated macrophages in NSCLC. Importantly, we report novel data on immune cell expression of the newly described CD200/CD200R1 pathway, and the leukocyte immunoglobulin-like receptors (LILRs), which may represent novel innate immune checkpoints, dampening the anti-tumor T cell immune response in NSCLC. Our study substantiates the importance of tumor-associated macrophages as a mediator of immunosuppression and a promising target for immunotherapy.

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CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy

Cited by 46 publications

References 59 publications

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

Analysis of Intra-Tumoral Macrophages and T Cells in Non-Small Cell Lung Cancer (NSCLC) Indicates a Role for Immune Checkpoint and CD200-CD200R Interactions

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