Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: A TAM-pting approach

Chamseddine, Ali N.; Assi, Tarek; Mir, Olivier; Chouaı̈b, Salem

doi:10.1016/j.pharmthera.2021.107986

Cited by 52 publications

(47 citation statements)

References 377 publications

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“…Macrophages in the surrounding TME are usually termed tumor-associated macrophages and include M1 and M2 macrophages [ 52 ]. Unlike tumor-associated M2 macrophages, which led to an immunosuppressive TME and are actively involved in cancer metastasis, M1 macrophages are usually used as drug carriers for tumor therapy that directly kills tumor cells [ 52 , 53 ]. Likewise, effector CD8 + T cells can inhibit tumor development and secrete several cytokines, including IFN- γ and IL-2 [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Gene Signature for Lower-Grade Gliomas Based on Pyroptosis-Related Genes to Predict Survival and Response to Immune Checkpoint Inhibitors

Lai

Deng

et al. 2022

Journal of Healthcare Engineering

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Pyroptosis plays a critical role in the immune response to immune checkpoint inhibitors (ICIs) by mediating the tumor immune microenvironment. However, the impact of pyroptosis-related biomarkers on the prognosis and efficacy of ICIs in patients with lower-grade gliomas (LGGs) is unclear. An unsupervised clustering analysis identified pyroptosis-related subtypes (PRSs) based on the expression profile of 47 pyroptosis-related genes in The Cancer Genome Atlas-LGG cohort. A PRS gene signature was established using univariate Cox regression, random survival forest, least absolute shrinkage and selection operator, and stepwise multivariable Cox regression analyses. The predictive power of this signature was validated in the Chinese Glioma Genome Atlas database. We also investigated the differences between high- and low-risk groups in terms of the tumor immune microenvironment, tumor mutation, and response to target therapy and ICIs. The PRS gene signature comprised eight PRS genes, which independently predicted the prognosis of LGG patients. High-risk patients had a worse overall survival than did the low-risk patients. The high-risk group also displayed a higher proportion of M1 macrophages and CD8+ T cells and higher immune scores, tumor mutational burden, immunophenoscore, IMmuno-PREdictive Score, MHC I association immune score, and T cell-inflamed gene expression profile scores, but lower suppressor cells scores, and were more suitable candidates for ICI treatment. Higher risk scores were more frequent in patients who responded to ICIs using data from the ImmuCellAI website. The presently established PRS gene signature can be validated in melanoma patients treated with real ICI treatment. This signature is valuable in predicting prognosis and ICI treatment of LGG patients, pending further prospective verification.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Gene Signature for Lower-Grade Gliomas Based on Pyroptosis-Related Genes to Predict Survival and Response to Immune Checkpoint Inhibitors

Lai

Deng

et al. 2022

Journal of Healthcare Engineering

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“…In pancreatic cancers, targeting CD47 efficiently enhanced the phagocytosis of tumor cells and the apoptosis of macrophages [ 230 ]. Efficiently blockade of the CD47-SIRPα pathway with genetically engineered cell-membrane-coated magnetic nanoparticles promoted the repolarization of M2-TAMs, triggering the potent immune responses in melanoma and breast cancer models [ 231 , 232 ]. Currently, the anti-CD47 monoclonal antibodies, including Hu5F9-G4, CC-9002, TI-061, and SRF231, are under clinical trial evaluation [ 233 ].…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

et al. 2022

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

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“…Arginine metabolism is critically related to TAM polarization [ 98 ]. The production of nitric oxide (NO) from arginine in M1 macrophages causes cytolysis of tumor cells, although M2 macrophages have increased enzymatic activities of arginase with a reduction in arginine levels and NO production [ 98 ]. Arginine is a critical amino acid involved in antitumor immunity involving the activation of T cells via T cell receptor upregulation [ 99 ].…”

Section: Crosstalk Between Tams and T Cells In Hccmentioning

confidence: 99%

Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma

Sung

2022

Clin Mol Hepatol

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The tumor microenvironment generally shows a substantial immunosuppressive activity in hepatocellular carcinoma (HCC), accounting for the suboptimal efficacy of immune-based treatments for this difficult-to-treat cancer. The crosstalk between tumor cells and various cell types in the tumor microenvironment is strongly related to HCC progression and treatment resistance. Monocytes are recruited to the HCC tumor microenvironment by various factors and become tumor-associated macrophages (TAMs) with distinct phenotypes. TAMs often contribute to weakened tumor-specific immune responses and a more aggressive phenotype of malignancy. Recent single-cell RNA-sequencing data have demonstrated the central roles of specific TAMs in tumorigenesis and treatment resistance by their interactions with various cell populations in the HCC tumor microenvironment. This review focuses on the roles of TAMs and the crosstalk between TAMs and neighboring cell types in the HCC tumor microenvironment.

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Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: A TAM-pting approach

Cited by 52 publications

References 377 publications

Identification and Validation of a Gene Signature for Lower-Grade Gliomas Based on Pyroptosis-Related Genes to Predict Survival and Response to Immune Checkpoint Inhibitors

Identification and Validation of a Gene Signature for Lower-Grade Gliomas Based on Pyroptosis-Related Genes to Predict Survival and Response to Immune Checkpoint Inhibitors

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma

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