Lipid-loaded macrophages as new therapeutic target in cancer

Marelli, Giulia; Morina, Nicolò; Portale, Federica; Pandini, Marta; Iovino, Marta; Conza, Giusy Di; Ho, Ping‐Chih; Mitri, Diletta Di

doi:10.1136/jitc-2022-004584

Cited by 21 publications

(16 citation statements)

References 114 publications

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“…Generally, increased lipid accumulation in TAMs is positively associated with their differentiation and function, especially because FAO is responsible for the downstream transcriptional regulation of several genes pertinent to TAM activity ( 7 , 8 ). By extension, several studies have shown that lipid accumulation in TAMs corresponds with tumor progression in a variety of cancer types ( 28 ). In gastric cancer, lipid accumulation in TAMs resulted in the upregulated expression of phosphoinositide 3-kinase (PI3K) -γ, which induced M2-like polarization ( 29 ).…”

Section: Lipids and Lipid Oxidation In Immune Cellsmentioning

confidence: 99%

Lipid metabolism in tumor immunology and immunotherapy

et al. 2023

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Lipids are a diverse class of biomolecules that have been implicated in cancer pathophysiology and in an array of immune responses, making them potential targets for improving immune responsiveness. Lipid and lipid oxidation also can affect tumor progression and response to treatment. Although their importance in cellular functions and their potential as cancer biomarkers have been explored, lipids have yet to be extensively investigated as a possible form of cancer therapy. This review explores the role of lipids in cancer pathophysiology and describes how further understanding of these macromolecules could prompt novel treatments for cancer.

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Section: Lipids and Lipid Oxidation In Immune Cellsmentioning

confidence: 99%

Lipid metabolism in tumor immunology and immunotherapy

et al. 2023

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“…As they play key roles in tumor development, macrophages are considered to be therapeutic targets. [38,39] In the TME, TAMs mainly have M2-like tumor-promoting effects and participate in various malignant characteristics, including immunosuppression and metastasis. [39,40] We analyzed the levels of various immune cells in the tissues of smoking and non-smoking NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

et al. 2023

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Lung cancer is a commonly diagnosed disease worldwide, with non-small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke is an environmental exposure promoting progression of NSCLC, but its role is poorly understood. This study reports that smoking-induced accumulation of M2-type tumor-associated macrophages (M2-TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette smoke extract (CSE)-induced M2 macrophages promoted malignancy of NSCLC cells in vitro and in vivo. circEML4 in EVs from CSE-induced M2 macrophages is transported to NSCLC cells, where it reduced the distribution of ALKBH5 in the nucleus by interacting with Human AlkB homolog H5 (ALKBH5), resulting in elevated N6-methyladenosine (m6A) modifications. m6A-seq and RNA-seq revealed suppressor of cytokine signaling 2 (SOCS2)-mediated activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by regulating m6A modification of SOCS2 via ALKBH5. Down-regulation of circEML4 in EVs from CSE-induced M2 macrophages reversed EVs-enhanced tumorigenicity and metastasis in NSCLC cells. Furthermore, this study found that smoking patients showed an increase in circEML4-positive M2-TAMs. These results indicate that smoking-induced M2-TAMs via circEML4 in EVs promote the NSCLC progression through ALKBH5-regulated m6A modification of SOCS2. This study also reveals that circEML4 in EVs from TAMs acts as a diagnostic biomarker for NSCLC, especially for patients with smoking history.

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“…ACOT9, which is abundant in monocytes, is an acyl-coenzyme A (CoA) thioesterase group that degrades acyl-CoA into CoA and fatty acids. Fat accumulation due to ACOT9 deficiency in tumor-associated macrophages may promote tumor growth and suppress immunity [ 28 ]. The four mRNAs proposed in this study may reflect the implications of

in a host immune capacity and NLR as an immune-suppression effect of cancer, from the perspective of past studies related to immune cells.…”

Section: Discussionmentioning

confidence: 99%

Exponential Slope from Absolute Lymphocyte Counts during Radio-Chemotherapy Can Predict an Aggressive Course of Cervical Cancer

Cho

Chun

Chang

2022

Cancers

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This study aimed to investigate whether the exponential slope α from absolute lymphocyte counts during concurrent radio–chemotherapy (CRT) is associated with aggressive and non-aggressive courses of cervical cancer. We analyzed 362 patients with stage IB–IVB cervical cancer treated with CRT in two groups: 323 patients without mRNA data (cohort 1) and 39 with mRNA data (cohort 2) from plasma exosomes. We calculated the α of each patient; 69 patients who died of cancer in cohort 1 were divided into 44 who died within 30 months (aggressive group), and 25 who died after more than 30 months (non-aggressive group). The median follow-up periods of cohorts 1 and 2 were 63 and 28 months, respectively. The log2 fold change (log2FC) between read counts of mRNAs before treatment and after the second week of CRT was calculated. Multivariate analyses from cohort 1 showed that neutrophil-to-lymphocyte ratio (NLR) ≥ 2.43 and α < 0.08 were statistically significant predictors of disease-specific survival (DSS) in the aggressive group (DSS-A), whereas α ≥ 0.08 was the only significant predictor of DSS in the non-aggressive group (DSS-NA). The 2.5-year DSS-A and 8-year DSS-NA rates of patients with α ≥ 0.08 and α < 0.08 were 86.7% and 73%, and 78.5% and 94.8% in the high-NLR group, respectively. In cohort 2, patients with both NLR < 2.7 and α ≥ 0.07 had a higher 2.5-year DSS rate than did those with either NLR ≥ 2.72 or α < 0.07. E2F8 and STX6 significantly correlated with ɑ and survival. The 2.5-year DSS rates in patients with E2F8 + STX6 (log2FC) < 0.2429 and ≥0.2429 were 100% and 77.2%, respectively. The exponential slope α can potentially distinguish between aggressive and non-aggressive courses in cervical cancer patients.

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Lipid-loaded macrophages as new therapeutic target in cancer

Cited by 21 publications

References 114 publications

Lipid metabolism in tumor immunology and immunotherapy

Lipid metabolism in tumor immunology and immunotherapy

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Exponential Slope from Absolute Lymphocyte Counts during Radio-Chemotherapy Can Predict an Aggressive Course of Cervical Cancer

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