The complex role of tumor-infiltrating macrophages

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(8), P. 1148 - 1156

Published: July 25, 2022

Language: Английский

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Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(9), P. 1660 - 1677.e10

Published: March 22, 2022

Language: Английский

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B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(7), P. 441 - 457

Published: April 1, 2022

Language: Английский

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Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 18, 2022

Abstract Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients refractory or resistant to these therapies, mechanisms underlying tumor resistance have not been fully elucidated. Immunosuppressive such as myeloid-derived suppressive cells, tumor-associated macrophages, neutrophils, regulatory (Tregs), dendritic critical factors correlated with resistance. In addition, cytokines secreted by immunosuppressive also mediate progression escape Thus, targeting related signals is promising therapy improve efficacy immunotherapies reverse even certain success in preclinical studies specific types cancer, large perspectives unknown therapies undesirable outcomes clinical patients. this review, we comprehensively summarized phenotype, function, potential targets microenvironment.

Language: Английский

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A timeline of tumour-associated macrophage biology

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 238 - 257

Published: Feb. 15, 2023

Language: Английский

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Cervical Cancer Immunotherapy: Facts and Hopes

Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 27(18), P. 4953 - 4973

Published: April 22, 2021

Abstract It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common to affect women worldwide. Persistent high-risk HPV (hrHPV) infection primary etiologic factor for cancer. Upward of 70% cases are driven by types 16 18, with dozen other hrHPVs associated remainder cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects limited efficacy against advanced disease. There few treatment options recurrent or metastatic Immunotherapy offers new hope, as demonstrated recent approval programmed cell death protein 1–blocking antibody This might be augmented combination antigen-specific immunotherapy approaches, such vaccines adoptive transfer, enhance host cellular immune response targeting HPV-positive cells. As progresses, it can foster an immunosuppressive microenvironment counteract anticancer immunity. Thus, approaches reverse suppressive environments bolster effector T-cell functioning likely success immunotherapy. The nonspecific immunostimulants like imiquimod genital warts also suggest possibility utilizing these immunotherapeutic strategies in prevention treat precursor lesions (cervical intraepithelial neoplasia) persistent hrHPV infections which licensed prophylactic no efficacy. Here, we review progress challenges development

Language: Английский

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Therapeutic targeting of tumour myeloid cells

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 216 - 237

Published: Feb. 6, 2023

Language: Английский

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Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment

Gut, Journal Year: 2022, Volume and Issue: 72(5), P. 958 - 971

Published: June 10, 2022

Innate immunity plays important roles in pancreatic ductal adenocarcinoma (PDAC), as non-T-cell-enriched tumour. Neutrophils are major players innate immune system. Here, we aimed to explore the heterogeneity and pro-tumour mechanisms of neutrophils PDAC.We analysed single-cell transcriptomes peripheral blood polymorphonuclear leucocytes (PMNs) tumour-infiltrating cells from five patients with PDAC, performed immunofluorescence/immunohistochemistry staining, multi-omics analysis vitro experiments validate discoveries bioinformatics analysis.Exploration tumour-associated (TANs) revealed a terminally differentiated subpopulation (TAN-1) associated poor prognosis, an inflammatory (TAN-2), population transitional stage that have just migrated tumour microenvironment (TAN-3) preferentially expressing interferon-stimulated genes (TAN-4). Glycolysis signature was upregulated along neutrophil transition trajectory, TAN-1 featured hyperactivated glycolytic activity. The switch TANs validated by integrative approach transcriptomics, proteomics metabolomics analysis. Activation activity LDHA overexpression induced immunosuppression functions neutrophil-like HL-60 (dHL-60) cells. Mechanistic studies BHLHE40, downstream hypoxia endoplasmic reticulum stress, key regulator polarisation towards phenotype, direct transcriptional regulation BHLHE40 on marker demonstrated chromatin immunoprecipitation assay. Pro-tumour were observed dHL-60 overexpressing BHLHE40. Importantly, immunohistochemistry PDAC tissues unfavourable prognostic value BHLHE40+ neutrophils.The dynamic properties this study will be helpful advancing therapy targeting immunity.

Language: Английский

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Cancer-Associated Fibroblasts in Inflammation and Antitumor Immunity

Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 29(6), P. 1009 - 1016

Published: Nov. 18, 2022

Abstract Tumor-associated inflammation (TAI) is a feature of essentially all cancers and can confer both tumor-promoting -suppressive functions. Cancer-associated fibroblasts (CAF) comprise one very heterogeneous cellular component the tumor microenvironment characterized by high degree plasticity. Recent single-cell sequencing analyses revealed distinct CAF populations in various human helped to define key subtypes, such as myofibroblastic, inflammatory, antigen-presenting CAFs, with first two being present virtually tumors. Importantly, these three are involved modulate positive negative consequences TAI. The remarkable plasticity CAFs allows them shift phenotypically functionally response environmental changes. In this review, we describe how nurture suppress adaptive immunity. We also summarize recently emerging evidence pertaining tumor-suppressive functions context Finally, therapeutic concepts that aim at modulating or depleting immunosuppressive synergize immunotherapy.

Language: Английский

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Metabolism drives macrophage heterogeneity in the tumor microenvironment

Cell Reports, Journal Year: 2022, Volume and Issue: 39(1), P. 110609 - 110609

Published: April 1, 2022

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, relationship between phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic from mice bearing liver metastatic tumors. find that manifest high heterogeneity at levels transcription, development, metabolism, function. Integrative analyses validation experiments indicate increased purine metabolism is feature with pro-tumor terminal differentiation phenotypes. Like mouse TAMs, human highly heterogeneous. Human exhibit correlate poor therapeutic efficacy to immune checkpoint blockade. Altogether, our work demonstrates developmentally, metabolically, functionally heterogeneous may be key macrophage population.

Language: Английский

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