SLC3A2 promotes tumor‐associated macrophage polarization through metabolic reprogramming in lung cancer

Cancer Science, Journal Year: 2023, Volume and Issue: 114(6), P. 2306 - 2317

Published: Feb. 16, 2023

Tumor-associated macrophages (TAMs) are one of the most abundant immunosuppressive cells in tumor microenvironment and possess crucial functions facilitating progression. Emerging evidence indicates that altered metabolic properties cancer support tumorigenic TAMs. However, mechanisms mediators underly cross-talk between TAMs remain largely unknown. In present study, we revealed high solute carrier family 3 member 2 (SLC3A2) expression lung patients was associated with poor prognosis. Knockdown SLC3A2 adenocarcinoma impaired M2 polarization a coculture system. Using metabolome analysis, identified knockdown metabolism changed multiple metabolites, including arachidonic acid, microenvironment. More importantly, showed acid responsible for SLC3A2-mediated macrophage to differentiate into type both vitro vivo. Our data illustrate previously undescribed TAM suggest acts as switch on induce phenotypic reprogramming through acid.

Language: Английский

---

Targeting lipid metabolism of macrophages: A new strategy for tumor therapy

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Lipid metabolism has been implicated in a variety of normal cellular processes and strongly related to the development multiple diseases, including tumor. Tumor-associated macrophage (TAM) emerged as crucial regulator tumorigenesis promising target for tumor treatment.

Language: Английский

---

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 84, P. 101952 - 101952

Published: May 3, 2024

Solute carrier (SLC), a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining metabolic demands cancer cells, promoting their survival, proliferation, adaptation to tumor microenvironment. Amino acids fundamental building blocks playing essential roles not only protein synthesis but also nutrient sensing, signaling pathways that can promote tumorigenesis. As key transporters SLCs have emerged as crucial players maintaining cellular acid homeostasis, dysregulation implicated various types. Thus, understanding intricate connections between SLCs, pivotal unraveling novel therapeutic targets strategies. uptake by positively affects progression. However, some studies revealed suppressor function SLCs. Although body evaluated SLC7A11 SLC1A5, SLC proteins studied sufficiently cancer. In this review, we delve into significant impact carriers on growth progression explore current state knowledge field, shedding light molecular mechanisms underlie these relationships highlighting potential avenues future research clinical interventions. comprehensive review provides insights rapidly evolving area biology focusing one most important materials cells need, within superfamily.

Language: Английский

---

CDKN2A^Lowcancer cells outcompete macrophages for microenvironmental zinc to drive immunotherapy resistance

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

ABSTRACT Approximately 50% of cancers exhibit decreased CDKN2A expression ( Low ), which is linked to immune checkpoint blockade (ICB) resistance. While traditionally recognized as a tumor suppressor and cell cycle regulator, we have previously put forth new paradigm demonstrating its role in intracellular metabolic reprogramming. Whether the derangement due loss alters metabolites within microenvironment (TME) how that affects compartment ICB response has never been investigated. Here found cancer cells reorganize zinc compartmentalization by upregulating importer SLC39A9 plasma membrane, leading accumulation concurrent depletion TME. This competition for results zinc-starved macrophages, reduced phagocytic activity. Remarkably, restoring levels TME through dietary intervention re-educates macrophages pro-phagocytic phenotype, sensitizing tumors ICB. Unexpectedly, T are not required this response. Clinically, from patients signatures, corresponding phagocytosis signatures. Moreover, with low circulating time-to-event outcomes compared those higher levels. Our work reveals unrecognized mechanism outcompete zinc, directly disrupting their function efficacy.

Language: Английский

---

The role of tumor-associated macrophages in lung cancer: From mechanism to small molecule therapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116014 - 116014

Published: Dec. 21, 2023

Tumor-associated macrophages (TAMs) are the main component of tumor-infiltrating immune cells in lung tumor microenvironment. TAMs recruited to cancer can create a suitable microenvironment for growth and metastasis by secreting promoting factors interfering with function T cells. Currently, numerous studies have reported that small molecular drugs affect progression selectively targeting TAMs. The ways include blocking recruitment monocytes or eliminating existing tissue, reprogramming into pro-inflammatory M1 inhibiting M2 polarization macrophages, interrupting interaction between modulating function. Signaling pathways cytokines such as CCL8, CCL2/CCR2, CSF-1/CSF-1R, STAT3, STAT6, MMPs, Caspase-8, AMPK α1, TLR3, CD47/SIRPα, been be involved this process. Based on summarizing role mechanisms progression, paper particularly focuses systematically reviewing effects molecule TAMs, classified according way they study aims provide new perspectives potential therapeutic targeted treatment cancer, which is great significance will more options immunotherapy cancer.

Language: Английский

---

Recreating metabolic interactions of the tumour microenvironment

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(6), P. 518 - 532

Published: Jan. 10, 2024

Language: Английский

---

Macrophage Polarisation in the Tumour Microenvironment: Recent Research Advances and Therapeutic Potential of Different Macrophage Reprogramming

Cancer Control, Journal Year: 2025, Volume and Issue: 32

Published: Jan. 1, 2025

Background Macrophages are a critical component of the innate immune system, derived from monocytes, with significant roles in anti-inflammatory and anti-tumour activities. In tumour microenvironment, however, macrophages often reprogrammed into tumour-associated (TAMs), which promote growth, metastasis, therapeutic resistance. Purpose To review recent advancements understanding macrophage polarisation reprogramming, highlighting their role progression potential as targets. Research Design This is article synthesising findings studies on reprogramming biology. Study Sample Not applicable (review existing literature). Data Collection and/or Analysis Key were identified summarised to explore mechanisms focusing M1/M2 polarisation, metabolic epigenetic changes, pathway regulation. Results Macrophage microenvironment involves complex mechanisms, including phenotypic functional alterations. These processes influenced by various signalling pathways. TAMs play pivotal progression, therapy resistance, making them prime targets for combination therapies. Conclusions Understanding underlying offers promising avenues developing therapies counteract progression. Future research should focus translating these insights clinical applications effective cancer treatment.

Language: Английский

---

Tumor microenvironment and drug resistance in lung adenocarcinoma: molecular mechanisms, prognostic implications, and therapeutic strategies

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 25, 2025

The fight against lung adenocarcinoma (LUAD) is challenged by tumor microenvironment (TME)-mediated drug resistance, which limits effective treatment. This study examines the LUAD TME and identifies four distinct subtypes through multi-omics profiling: immune-rich, immune-exhausted, stromal-dominant, TME-desert. Each subtype has unique molecular features, diversity, links to clinical outcomes. Immune-rich respond better immune checkpoint inhibitors, while stromal-dominant TME-desert show resistance treatment poor prognosis. Molecular analysis uncovers subtype-specific mutations, chromosomal instability, altered signaling pathways, pointing potential therapeutic targets. In silico screening promising treatments for resistant subtypes. These findings, validated in independent cohorts, highlight critical role of response, providing insights personalized strategies LUAD.

Language: Английский

---

Thrombospondin-2 induces M2 macrophage polarization through fatty acid metabolism to drive lung adenocarcinoma proliferation

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as tumor marker and is known to be overexpressed LUAD. However, specific THBS2 M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses assess clinical significance expression LUAD, which was subsequently validated using quantitative PCR. examined relationship between infiltration. A coculture system cells M0 established investigate influence on infiltration through immunofluorescence ELISA. explored impact fatty acid metabolism (FAM) oil red O staining relevant kits elucidated proliferation cell counting kit-8 (CCK-8) colony formation assays. Western blot employed changes Bax Bcl-2. highly expressed associated with poor prognosis patients. In-vitro experiments demonstrated that silencing significantly inhibited polarization. primarily activated FAM pathways, inducing promoting proliferation. enhanced by induce These findings provide theoretical basis for targeting novel therapeutic strategy

Language: Английский

---

Biological mechanisms and immunotherapy of brain metastases in non-small cell lung cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189320 - 189320

Published: April 1, 2025

Language: Английский

---