IFNγ signaling integrity in colorectal cancer immunity and immunotherapy

Du, Wei; Frankel, Timothy L.; Green, Michael; Zou, Weiping

doi:10.1038/s41423-021-00735-3

Cited by 85 publications

(53 citation statements)

References 123 publications

(134 reference statements)

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“…On the other hand, analysis results indicated that the interferon-γ (IFN-γ) response pathway was negatively correlated with glycerolipid metabolism in colon cancer. The IFN-γ signaling pathway plays a critical role in anticancer immunity mainly through anti-proliferation ( 38 ), apoptosis ( 39 ), necrosis ( 40 ), and ferroptosis ( 41 ); however, it is also reported that IFN-γ induces the expression of immune checkpoints which may lead to an immune-suppression microenvironment, and this was consistent with our further analysis about the immune microenvironment ( 42 – 44 ). Taken together, our results suggested that the IFN-γ response pathway might mainly contribute to the immune-suppression microenvironment in glycerolipid metabolism-activated colon cancer, other than antitumor effect.…”

Section: Discussionsupporting

confidence: 90%

Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer

Wang

Zhang

et al. 2022

Front. Oncol.

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BackgroundGlycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics.MethodsClinical information and mRNA expression data of patients with colon cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the glycerolipid metabolism-related gene enrichment score (GLMS). Univariable and multivariable Cox regression analyses were used to study the prognostic value of GLMS in TCGA-COAD and GSE39582 cohorts. The molecular mechanism of the prognostic factor was investigated via immune cell infiltration estimation and correlation analysis of cancer hallmark pathways. Single-cell transcriptomic dataset GSE146771 was used to identify the cell populations which glycerolipid metabolism targeted on.ResultsThe GLMS was found to be associated with tumor location and consensus molecular types (CMSs) of colon cancer in TCGA-COAD cohort (P < 0.05). Patients in the low-GLMS group exhibited poorer overall survival (OS) in TCGA cohort (P = 0.03; HR, 0.63; 95% CI, 0.42–0.94), which was further validated in the GSE39582 dataset (P < 0.001; HR, 0.57; 95% CI, 0.43–0.76). The association between the GLMS and OS remained significant in the multivariable analysis (TCGA cohort: P = 0.04; HR, 0.64; 95% CI, 0.42–0.98; GSE39582 cohort: P < 0.001; HR, 0.60; 95% CI, 0.45–0.80). The GLMS was positively correlated with cancer hallmark pathways including bile acid metabolism, xenobiotic metabolism, and peroxisome and negatively correlated with pathways such as interferon gamma response, allograft rejection, apoptosis, and inflammatory response (P < 0.05). Increased immune infiltration and upregulated expression of immune checkpoints were observed in patients with lower GLMS (P < 0.05). Single-cell datasets verified the different distribution of GLMS in cell subsets, with significant enrichment of GLMS in malignant cells and Tprolif cells.ConclusionWe demonstrated that GLMS was a potential independent prognostic factor for colon cancer. The GLMS was also correlated with several cancer hallmark pathways, as well as immune microenvironment.

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Section: Discussionsupporting

confidence: 90%

Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer

Wang

Zhang

et al. 2022

Front. Oncol.

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“…These modified phospholipids are more sensitive to oxidative damage and thereby enhance tumor sensitivity to ferroptosis [33,34]. Additionally, IFNγ can also enhance the tumor-eliminating potential of CD8+ T cells in a wide range of malignancies, suggesting a positive feedback between CD8+ T cells and IFNγ [35]. Nonetheless, it requires further investigation whether CD8+ T cells could trigger ferroptosis in a IFN-γ-independent manner.…”

Section: Ferroptosis Within the Timementioning

confidence: 99%

Targeting the Macrophage-Ferroptosis Crosstalk: A Novel Insight into Tumor Immunotherapy

Shi¹,

Xu²,

Hu³

et al. 2022

Front. Biosci. (Landmark Ed)

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Ferroptosis is an emerging form of non-apoptotic, regulated cell death that is mechanistically dependent on aberrant iron accumulation and excessive lipid peroxidation. Further evidence indicates that ferroptosis plays a crucial role in the efficacy of tumor immunotherapy. Ferroptosis is often constrained by tumor-associated macrophages (TAMs), and this poses a challenge to clinicians aiming to exploit the potency of immunotherapy to treat various forms of cancer. Current advances revealed a dual character to TAMs in regulating tumor ferroptosis. Specifically, some signaling molecules released from cells undergoing ferroptosis can exert effects on TAM polarization. In this review, we summarize the currently characterized mechanisms of macrophage-ferroptosis crosstalk, discuss how macrophageferroptosis crosstalk affects the outcome of tumor immunotherapy, and provide an overview of current advances that seek to leverage this crosstalk to improve cancer immunotherapy efficacy. Despite the fact that further efforts are still required to achieve a more comprehensive understanding of the mechanisms that control this signaling, targeting macrophage-ferroptosis crosstalk has clear potential for reversing immunotherapeutic resistance and may shed light on new therapeutic strategies to overcome some advanced and metastatic malignancies.

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“…human interferon (IFN-γ) plays a role in immune evasion and tumor growth, as it stimulates the expression of immunosuppressive molecules, such as B7-H1 (PD-L1), arginase, and indoleamine 2,3-dioxygenase (IDO), in the tumor microenvironment (Diskin et al, 2020). IFN-γ signaling plays a therapeutic role because it enhances the immune system against cancer by inhibiting the growth of many cancer cells including breast cancer cells (García-Tuñón et al, 2007), and It has also a role in promoting cancer development and immune evasion, so IFN-γ is considered to have a dual role (Du et al, 2021).…”

Section: Il-1βmentioning

confidence: 99%

relationship between cellular mediators (IL-1β, IFN–γ, MMP-9) in Iraqi women with breast cancer

Al-Mashhadani

Alabassi

Mahood

2022

ijhs

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Breast cancer is the most common type of cancer in Iraq. The incidence of breast cancer has increased among Iraqi women in the past two decades, as it represents one of the main threats to women's health. This steady aimed To evaluate the level of some immune factors Interleukin-1β (IL-1β), Interferon- γ (IFN–γ), and Matrix metalloproteinase-9 (MMP-9), and find the relationship between these immune factors in Iraqi women diagnosed with breast cancer. Material and method Fifty women diagnosed with breast cancer were enrolled in this study in addition to 25 healthy individuals as a control group. Level (IL-1β, IFN-γ, MMP-9) was measured using ELISA technology. Conclusion The expression level of (IL-1β, IFN-γ, MMP-9) increased in women with breast cancer in different age groups, but the age group (40-49) also recorded the highest expression of these cellular mediators. Regarding the relationship of (MMP-9), it was not significant with (IL-1β), but it was significant with (IFN-γ) (p≤0.05), and about the relationship between (IL-1β) and (IFN-γ) it was no significant negatively, that Increased level of (IL-1β, IFN-γ, MMP-9) expression could be a predictive marker of breast cancer.

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IFNγ signaling integrity in colorectal cancer immunity and immunotherapy

Cited by 85 publications

References 123 publications

Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer

Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer

Targeting the Macrophage-Ferroptosis Crosstalk: A Novel Insight into Tumor Immunotherapy

relationship between cellular mediators (IL-1β, IFN–γ, MMP-9) in Iraqi women with breast cancer

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