Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

Davidov, Vitaliy; Jensen, Garrett L; Mai, Sunny; Chen, Shu‐Hsia; Pan, Ping-Ying

doi:10.3389/fimmu.2020.01842

Cited by 31 publications

(32 citation statements)

References 209 publications

(280 reference statements)

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“…In tissue-resident macrophages, such as in a normal human lung, CD206 is ubiquitously expressed in macrophage populations [ 22 , 23 ], and in the dominating M2-polarized population of TAMs in NSCLC [ 24 ]. We did not include CD14 in the gating strategy, as this might have excluded immunosuppressive myeloid cells with low expression of CD14 [ 25 , 26 ]. Sorted immune cells were collected in Roswell Park Memorial Institute medium 1640 (RPMI, Sigma-Aldrich Corp, St. Louis, MO, USA) supplemented with 30% FCS in sterile polypropylene tubes (Corning).…”

Section: Methodsmentioning

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

Tøndell

Subbannayya

Wahl

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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Section: Methodsmentioning

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

Tøndell

Subbannayya

Wahl

et al. 2021

Cancers

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“…All tumors exhibit a complex landscape of myeloid cells which are, among other cells, responsible for therapeutic responses [ 60 ]. Tumor cells and tumor-associated fibroblasts drive cancer-associated myelopoiesis by secreting soluble factors leading to the recruitment and expansion of myeloid cells from the bone marrow.…”

Section: Recruitment and Polarization Of M-mdscs And Macrophagesmentioning

confidence: 99%

Tumor-Associated Macrophages—Implications for Molecular Oncology and Imaging

et al. 2021

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Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting in varying membrane receptors and expression of intracellular proteins allow the specific characterization of different subsets of TAMs. Those markers similarly allow tracking of TAMs by different means of molecular imaging. This review aims to provides an overview of the origin of tumor-associated macrophages, their polarization in different subtypes, and how characteristic markers of the subtypes can be used as targets for molecular imaging and theranostic approaches.

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“…Suppressive myeloid cells can also be reprogrammed into their immunostimulatory counterparts by a range of therapeutics. These strategies typically function by blocking receptors inducing inhibitory signals or by providing exogenous ligands for receptors activating pro-inflammatory pathways [192]. One strategy to repolarize myeloid cells is targeting histone deacetylase (HDAC) proteins or epigenetic reader proteins [193,194].…”

Section: Repolarization Of Myeloid Cellsmentioning

confidence: 99%

Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment

Frosch

Leontari

Anderson

2021

Cancers

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Despite multimodal treatment, survival chances for high-risk neuroblastoma patients remain poor. Immunotherapeutic approaches focusing on the activation and/or modification of host immunity for eliminating tumor cells, such as chimeric antigen receptor (CAR) T cells, are currently in development, however clinical trials have failed to reproduce the preclinical results. The tumor microenvironment is emerging as a major contributor to immune suppression and tumor evasion in solid cancers and thus has to be overcome for therapies relying on a functional immune response. Among the cellular components of the neuroblastoma tumor microenvironment, suppressive myeloid cells have been described as key players in inhibition of antitumor immune responses and have been shown to positively correlate with more aggressive disease, resistance to treatments, and overall poor prognosis. This review article summarizes how neuroblastoma-driven inflammation induces suppressive myeloid cells in the tumor microenvironment and how they in turn sustain the tumor niche through suppressor functions, such as nutrient depletion and generation of oxidative stress. Numerous preclinical studies have suggested a range of drug and cellular therapy approaches to overcome myeloid-derived suppression in neuroblastoma that warrant evaluation in future clinical studies.

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Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

Cited by 31 publications

References 209 publications

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

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

Tumor-Associated Macrophages—Implications for Molecular Oncology and Imaging

Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment

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