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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Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1112 - 1140

Published: Sept. 7, 2022

Abstract Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor‐associated macrophages (TAMs) are among most abundant immune cells infiltrating TME and present at all stages cancer progression, targeting TAMs has become one favored immunotherapy strategies. In addition, distinct origins. At early stage cancer, can provide niche for maintenance stem cells. contrast, (CSCs) or poorly differentiated key factors modulating macrophage activation. review, we first propose origin connection between precursor Macrophages undergo dynamic phenotypic transition during carcinogenesis. this course such transition, it is critical to determine appropriate timing therapy block specific markers suppress pro‐tumoral TAMs. The review provides more detailed discussion trends surface than previous reviews. Complex crosstalk occurs play indispensable roles angiogenesis, autophagy due their heterogeneity robust plasticity. interact with other by directing cell‐to‐cell contact secreting various effector molecules. Similarly, combined drive recruitment polarization. Despite latest achievements advancements treatment strategies following studies, comprehensive discussions on communication currently lacking. discussed interactions (from cell maturation), therapeutic (including chimeric antigen receptor macrophages), clinical trials hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (iCCA) rationale further investigation as potential target treating patients

Language: Английский

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RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

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The roles and implications of RNA m6A modification in cancer

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 507 - 526

Published: May 23, 2023

Language: Английский

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Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 3, 2022

Anti-programmed cell death 1 (PD-1) or anti-PD-ligand (L) drugs, as classic immune checkpoint inhibitors, are considered promising treatment strategies for tumors. In clinical practice, some cancer patients experience drug resistance and disease progression in the process of anti-PD-1/PD-L1 immunotherapy. Tumor-associated macrophages (TAMs) play key roles regulating PD-1/PD-L1 immunosuppression by inhibiting recruitment function T cells through cytokines, superficial ligands, exosomes. There several therapies available to recover anticancer efficacy inhibitors targeting TAMs, including inhibition TAM differentiation re-education activation. this review, we will summarize mechanisms TAMs blocker resistance. Furthermore, discuss that were designed deplete re-educate intervene with chemokines secreted exosomes from M1 macrophages, providing more potential options improve inhibitors.

Language: Английский

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Roles of tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for solid cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 21, 2023

Abstract In recent years, tumor immunotherapy has made significant progress. However, immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny proportion of patients in solid cancers. The microenvironment (TME) acts role immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one the main components TME, seriously affected therapeutic effect inhibitors. this review, we analyzed TAMs from epigenetic and single-cell perspectives introduced mechanisms anti-programmed death protein 1(anti-PD-1) therapy. addition, summarized combination regimens enhance efficacy elaborated on different Eventually, clinical value by influencing was discussed. These above are beneficial to elucidate poor tumors point view explore strategies improve its objective remission rate

Language: Английский

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Targeting the RNA m6A modification for cancer immunotherapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: March 16, 2022

Abstract N 6 -methyladenosine (m A) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription translation programs that promote cancer occurrence progression. Although defective gene regulation resulting from m A often affects oncogenic tumor-suppressing networks, can also modulate tumor immunogenicity immune cells involved in anti-tumor responses. Understanding this counterintuitive concept aid design new drugs target to potentially improve outcomes immunotherapies. Here, we provide an up-to-date comprehensive overview how modifications intrinsically affect alterations cell extrinsically responses microenvironment (TME). We review strategies for modulating endogenous immunity discuss challenge reshaping TME. Strategies include: combining specific efficient inhibitors against regulators with checkpoint blockers; generating effective programmable gene-editing system enables manipulation individual sites; establishing enhance T or natural killer cells; using nanoparticles specifically tumor-associated macrophages (TAMs) deliver messenger RNA small interfering A-related molecules repolarize TAMs, enabling them remodel The goal help field understand shape TME so better immunotherapy be designed developed.

Language: Английский

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METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 14, 2022

Abstract Background N6-methyladenosine (m 6 A) RNA methylation and circular RNAs (circRNAs) have been shown to act vital roles in multiple malignancies including gastric cancer (GC). However, there is little knowledge about how m A modification of circRNAs contributes GC progression. Methods The association METTL14 expression with the clinicopathological characteristics prognosis patients was assessed by Western blot, Immunohistochemistry public datasets. In vitro vivo function experiments were conducted investigate role GC. Furthermore, A-circRNA epitranscriptomic microarray utilized identify METTL14-mediated circRNAs, which validated methylated immunoprecipitation (Me-RIP), RT-qPCR rescue cells. sponge circORC5 miR-30c-2-3p confirmed luciferase gene report assays. expression, localization evaluated fluorescence situ hybridization. effects (or) on miR-30c-2-3p-mediated AKT1S1 EIF4B estimated blot analyses. Results We found that downregulated tissue samples its low acted as a prognostic factor poor survival Ectopic markedly repressed growth invasion cells , whereas knockdown harbored opposite effects. Mechanically, Me-RIP identified downstream target METTL14. Silencing reduced level circORC5, but increased expression. Moreover, could miR-30c-2-3p, reverse METTL14-caused upregulation downregulation EIF4B. addition, possessed negative correlation indicated Conclusion Our findings demonstrate suppresses progression regulating miR-30c-2-3p/AKT1S1 axis.

Language: Английский

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Refining colorectal cancer classification and clinical stratification through a single-cell atlas

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: May 10, 2022

Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms stroma cell contributions pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples analyze multiple independent external cohorts for a total 487,829 single cells enabling high-resolution depiction the cellular diversity heterogeneity within microenvironmental cells.Tumor recapitulate individual subgroups yet exhibit significant intratumoral heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs stable (MSS) demonstrate similar pathway activations at epithelial level. However, CD8+ cytotoxic T phenotype infiltration in MSI-H explain why these tumors respond immune checkpoint inhibitors. Cellular transcriptomic profiles exist continuum contrast discrete proposed by studies utilizing bulk transcriptomics. note dichotomy across exists patients with high cancer-associated fibroblasts (CAFs) C1Q+TAM content poor outcomes, providing higher level personalization precision than would distinct subtypes. Additionally, we discover CAF known be associated immunotherapy resistance.Distinct CAFs C1Q+ TAMs are sufficient predictive ability simpler signature based on phenotypes could stratify patient prognosis greater precision. Therapeutically targeting specific C1Q + promote responses patients.

Language: Английский

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YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 255 - 266

Published: Jan. 19, 2023

Language: Английский

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