CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Ma, Xingzhe; Xiao, Liuling; Liu, Lintao; Ye, Lingqun; S, Pan; Bi, Enguang; Wang, Qiang; Yang, Mengjiao; Qian, Jianfei; Yi, Qing

doi:10.1016/j.cmet.2021.02.015

Cited by 390 publications

(227 citation statements)

References 46 publications

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“…It indicates the association of ferroptosis signature and glioma immunity. In fact, there were several previous investigations supporting that intervention of ferroptosis process had a significant effect on cancer immunotherapy 13,53 . Deficiency of the FRG (SLC7A11) in mice with melanoma was more susceptible to anti‐PD‐L1 therapy, 54 which suggests again the role of ferroptosis in anti‐tumor immunity.…”

Section: Discussionmentioning

confidence: 93%

“…In fact, there were several previous investigations supporting that intervention of ferroptosis process had a significant effect on cancer immunotherapy. 13 , 53 Deficiency of the FRG (SLC7A11) in mice with melanoma was more susceptible to anti‐PD‐L1 therapy, 54 which suggests again the role of ferroptosis in anti‐tumor immunity. The evidence supporting the role of FRGs in tumor immunity also arises from the study that T cells lacking GPX4 failed to expand and they rapidly underwent ferroptotic cell death.…”

Section: Discussionmentioning

confidence: 98%

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Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma

et al. 2021

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Aims Glioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death is promising in cancer therapy. Ferroptosis, a recently discovered regulated cell death, can be induced for killing glioma cells. However, the prognostic prediction of ferroptosis‐related genes (FRGs) in glioma remains elusive. Methods The mRNA expression profiles and gene variation and corresponding clinical data of glioma patients and NON‐TUMOR control were downloaded from public databases. Risk score based on a FRGs signature was constructed in REMBRANDT cohort and validated in other datasets including CGGA‐693, CGGA‐325, and TCGA. Results Our results demonstrated that the majority of FRGs was differentially expressed among GBM, LGG, and NON‐TUMOR groups (96.6%). Furthermore, the glioma patients with low‐risk score exhibited a more satisfactory clinical outcome. The better prognosis was also validated in the glioma patients with low‐risk score no matter to which grade they were affiliated. Functional analysis revealed that the high‐risk score group was positively correlated with the enrichment scores for immune checkpoint blockade‐related positive signatures, indicating the critical role of glioma immunotherapy via risk score. Conclusion A novel FRGs‐related risk score can predict prognosis and immunotherapy in glioma patients.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma

et al. 2021

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“…Cytotoxic CD8 + T cells are killer cells in the T lymphocyte population. They support a large amount of cellular immunity, especially in tumour tissues (23,24). CD4 + T cells play an important role in the activation and memory of cytotoxic CD8 + T cells (25).…”

Section: Discussionmentioning

confidence: 99%

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

Zhou

Liu

et al. 2021

Front. Immunol.

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BackgroundCD161, encoded by killer cell lectin-like receptor B1 gene, is a newly reported candidate inhibitor of tumour-infiltrating T cells. Antibody-mediated CD161 blockade enhances T cell-mediated killing of cancer cells in vitro and in vivo in several tumour types. We evaluated the role of CD161 using The Cancer Genome Atlas (TCGA) Pan-Cancer Data.MethodsCD161 expression was analysed using RNAseq data from TCGA and the Genotype-Tissue Expression (GTEx) database. HPA, GeneCards, and String database were used to explore the protein information of CD161. The prognostic value of CD161 was analysed using clinical survival data from the TCGA. Enrichment analysis of CD161 was conducted using the R package “clusterProfiler”. We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CD161 expression. We further assessed the association between CD161 and immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.FindingsCD161 was differentially expressed and predicted better survival status in most tumour types in TCGA. In addition, CD161 expression was significantly associated with immunoregulatory interactions between lymphoid and non-lymphoid cells. CD161 expression was closely correlated with T cell infiltration, immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.InterpretationOur results suggest that CD161 is a potential cancer biomarker. CD161 might synergize with other immune checkpoints to regulate the immune microenvironment, which could be applied in the development of new-targeted drugs for immunotherapy.FundingThis work was supported by the National Nature Science Foundation of China (grant numbers 81773008, 81672756, 81872399, 81972897), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015), the Natural Science Foundation of Guangdong Province (grant number 2017A030311023), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program: 2017BT01S131 and the Guangzhou Technology Project (grant number 201804010044), National Key R&D Program of China (Grant Nos. 2020YFC2006400), Key-Area Research and Development Program of Guangdong Province (2019B020227004).

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“…Other signaling molecules, such as ACSL4 and AMP-activated protein kinase (AMPK), have been linked to both mTORC1 and ferroptosis, [6,[85][86][87][88][89] raising the question of whether ACSL4 or AMPK is also involved in the cross-talks between mTORC1 and ferroptosis. In addition, both mTORC1 and ferroptosis have been linked with immune system functions; [31,[90][91][92] therefore, it will be interesting to further understand the effects of mTOR inhibitors in combination with FINs on tumor immunity. Finally, although we have focused on cancer in this review, it is important to note that aberrant mTORC1 signaling also contributes to several other diseases or pathological conditions, such as aging, epileptic seizures, and Alzheimer disease.…”

Section: Discussionmentioning

confidence: 99%

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

Lei

Gan

2021

BioEssays

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Ferroptosis, a form of regulated cell death triggered by lipid hydroperoxide accumulation, has an important role in a variety of diseases and pathological conditions, such as cancer. Targeting ferroptosis is emerging as a promising means of therapeutic intervention in cancer treatment. Polyunsaturated fatty acids, reactive oxygen species, and labile iron constitute the major underlying triggers for ferroptosis. Other regulators of ferroptosis have also been discovered recently, among them the mechanistic target of rapamycin complex 1 (mTORC1), a central controller of cell growth and metabolism.Inhibitors of mTORC1 have been used in treating diverse diseases, including cancer. In this review, we discuss recent findings linking mTORC1 to ferroptosis, dissect mechanisms underlying the establishment of mTORC1 as a key ferroptosis modulator, and highlight the potential of co-targeting mTORC1 and ferroptosis in cancer treatment. This review will provide valuable insights for future investigations of ferroptosis and mTORC1 in fundamental biology and cancer therapy.

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CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Cited by 390 publications

References 46 publications

Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma

Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

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