A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications

Sedighzadeh, Sahar; Khoshbin, Amin Pastaki; Razi, Sepideh; Keshavarz-Fathi, Mahsa; Rezaei, Nima

doi:10.21037/tlcr-20-1241

Cited by 96 publications

(70 citation statements)

References 277 publications

(222 reference statements)

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“…Macrophages, especially tumor-associated macrophage (TAM), are crucial immunocytes in the lung cancer microenvironment, accounting for a notable proportion, up to 50% in a variety of solid tumors ( Li et al, 2018 ; Singhal et al, 2019 ; Larionova et al, 2020 ; Sedighzadeh et al, 2021 ). Their actions in promoting immunosuppression in lung cancer by releasing immunosuppressive cytokines, reduction of cytotoxic lymphocyte infiltration, and increasing the ratio of regulatory T cells (Treg) contribute to the failure of eradicating lung cancer ( Economopoulou and Mountzios, 2018 ; Xu et al, 2020 ; Sarode et al, 2020 ; La Fleur et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Chlorin e6-Induced Photodynamic Effect Polarizes the Macrophage Into an M1 Phenotype Through Oxidative DNA Damage and Activation of STING

Han

et al. 2022

Front. Pharmacol.

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The tumor-associated macrophage (TAM) serves as an immunosuppressive agent in the malignant tumor microenvironment, facilitating the development and metastasis of lung cancer. The photodynamic effect destabilizes cellular homeostasis owing to the generation of reactive oxygen species (ROS), resulting in the enhanced pro-inflammatory function of immunocytes. In our previous study, the Ce6-mediated photodynamic effect was found to have kept the viability of macrophages and to remodel them into the M1 phenotype. However, the mechanism remains unrevealed. The present study now explores the mechanism of photodynamic therapy (PDT)-mediated reprogramming of macrophages. As expected, Ce6-mediated PDT was capable of generating reactive oxygen species, which was continuously degraded, causing “low intensity” damage to DNA and thereby triggering subsequent DNA damage response in macrophages. The autophagy was thus observed in Ce6-treated macrophages and was shown to protect cells from being photodynamically apoptotic. More importantly, Ce6 PDT could activate the stimulator of interferon genes (STING) molecule, a sensor of DNA damage, which could activate the downstream nuclear factor kappa-B (NF-κB) upon activation, mediating the polarization of macrophages towards the M1 phenotype thereupon. In addition, inhibition of ROS induced by PDT attenuated the DNA damage, STING activation, and M1-phenotype reprogramming. Furthermore, the silence of the STING weakened Ce6 treatment-mediated M1 remodeling of macrophages as well. Altogether, these findings indicate the Ce6-induced photodynamic effect polarizes macrophages into an M1 phenotype through oxidative DNA damage and subsequent activation of the STING. This work reveals the crucial mechanism by which photodynamic therapy regulates the macrophage phenotype and also provides a novel intervenable signaling target for remodeling macrophages into the M1 phenotype.

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Section: Introductionmentioning

confidence: 99%

Chlorin e6-Induced Photodynamic Effect Polarizes the Macrophage Into an M1 Phenotype Through Oxidative DNA Damage and Activation of STING

Han

et al. 2022

Front. Pharmacol.

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“…It has also been reported that TAMs contribute to lung cancer progression, angiogenesis, invasion, metastasis, immunosuppression, and resistance to chemotherapy by releasing cytokines, growth factors, and chemokines [56]. Studies in lung cancer have shown that TAMs express M1 markers during tumor formation and switch to the M2 phenotype during lung cancer progression [57,58]. Several studies have found that having a high density of M2 phenotype TAMs in the TME correlated with poor survival in lung cancer [59][60][61].…”

Section: Role Of Tams In Lung Cancermentioning

confidence: 99%

Hidden Treasures: Macrophage Long Non-Coding RNAs in Lung Cancer Progression

Karger

Nandigama

Grimminger

et al. 2021

Cancers

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Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as “junk” in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis. In this review, we aimed to describe the complex roles and functions of lncRNAs in macrophages and their influence on lung cancer development and progression through the TME.

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“…Downregulation of Mir-183-5p reversed the M2-TAMs mediated tumor promotion ( Zhang et al, 2021a ). In some clinical studies of non-small cell lung cancer, M2-TAMs infiltrate induce tumor cell invasion and progression, resulting in poor prognosis ( Sumitomo et al, 2019 ; Sedighzadeh et al, 2021 ). Pulmonary macrophage accumulation is one of the important factors leading to lung metastasis of ATC ( Li et al, 2016 ).…”

Section: Tumor-associated Macrophages In the Thyroid Tumor Microenvir...mentioning

confidence: 99%

Roles and new Insights of Macrophages in the Tumor Microenvironment of Thyroid Cancer

2022

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Although most thyroid cancers have a good and predictable prognosis, the anaplastic, medullary, and refractory thyroid cancers still prone to recurrence and metastasis, resulting in poor prognosis. Although a number of newly developed targeted therapies have begun to be indicated for the above types of thyroid cancer in recent years, their ability to improve overall survival remain hindered by low efficacy. As the largest component of immune cells in tumor microenvironment, tumor-associated macrophages play a key role in the invasion and metastasis of thyroid cancer. There is much evidence that the immune system, tumor microenvironment and cancer stem cell interactions may revolutionize traditional therapeutic directions. Tumor-associated macrophages have been extensively studied in a variety of tumors, however, research on the relationship between thyroid cancer and macrophages is still insufficient. In this review, we summarize the functions of tumor-associated macrophages in different types of thyroid cancer, their cytokines or chemokines effect on thyroid cancer and the mechanisms that promote tumor proliferation and migration. In addition, we discuss the mechanisms by which tumor-associated macrophages maintain the stemness of thyroid cancer and potential strategies for targeting tumor-associated macrophages to treat thyroid cancer.

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A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications

Cited by 96 publications

References 277 publications

Chlorin e6-Induced Photodynamic Effect Polarizes the Macrophage Into an M1 Phenotype Through Oxidative DNA Damage and Activation of STING

Chlorin e6-Induced Photodynamic Effect Polarizes the Macrophage Into an M1 Phenotype Through Oxidative DNA Damage and Activation of STING

Hidden Treasures: Macrophage Long Non-Coding RNAs in Lung Cancer Progression

Roles and new Insights of Macrophages in the Tumor Microenvironment of Thyroid Cancer

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