Roles of macrophages on ulcerative colitis and colitis-associated colorectal cancer

Zhang, Maorun; Li, Xiaoping; Zhang, Qi; Yang, Jingsi; Liu, Gang

doi:10.3389/fimmu.2023.1103617

Cited by 33 publications

(15 citation statements)

References 130 publications

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“…Our findings revealed that the high-risk group had a predominant enrichment of macrophages and pDCs, while the low-risk group had a predominant enrichment of Th2 cells. It has been reported that high infiltration of macrophages exacerbates the progression of ulcerative colitis to colon cancer and is considered a poor prognostic marker 52 , 53 . Similarly, extensive infiltration of pDCs predicts a poor prognosis in breast and ovarian cancer 54 , 55 .…”

Section: Discussionmentioning

confidence: 99%

Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis

Xie,

Li,

Tao

et al. 2024

J. Cancer

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Backgrounds: Colorectal cancer (CRC) is a highly malignant gastrointestinal malignancy with a poor prognosis, which imposes a significant burden on patients and healthcare providers globally. Previous studies have established that genes related to glutamine metabolism play a crucial role in the development of CRC. However, no studies have yet explored the prognostic significance of these genes in CRC. Methods: CRC patient data were downloaded from The Cancer Genome Atlas (TCGA), while glutamine metabolism-related genes were obtained from the Molecular Signatures Database (MSigDB) database. Univariate COX regression analysis and LASSO Cox regression were utilized to identify 15 glutamine metabolism-related genes associated with CRC prognosis. The risk scores were calculated and stratified into high-risk and low-risk groups based on the median risk score. The model's efficacy was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve analysis. Cox regression analysis was employed to determine the risk score as an independent prognostic factor for CRC. Differential immune cell infiltration between the high-risk and low-risk groups was assessed using the ssGSEA method. The clinical applicability of the model was validated by constructing nomograms based on age, gender, clinical staging, and risk scores. Immunohistochemistry (IHC) was used to detect the expression levels of core genes. Results: We identified 15 genes related to glutamine metabolism in CRC: NLGN1, RIMKLB, UCN, CALB1, SYT4, WNT3A, NRCAM, LRFN4, PHGDH, GRM1, CBLN1, NRG1, GLYATL1, CBLN2, and VWC2. Compared to the high-risk group, the low-risk group demonstrated longer overall survival (OS) for CRC. Clinical correlation analysis revealed a positive correlation between the risk score and the clinical stage and TNM stage of CRC. Immune correlation analysis indicated a predominance of Th2 cells in the low-risk group. The nomogram exhibited excellent discriminatory ability for OS in CRC. Immunohistochemistry revealed that the core gene CBLN1 was expressed at a lower level in CRC, while GLYATL1 was expressed at a higher level. Conclusions: In summary, we have successfully identified and comprehensively analyzed a gene signature associated with glutamine metabolism in CRC for the first time. This gene signature consistently and reliably predicts the prognosis of CRC patients, indicating its potential as a metabolic target for individuals with CRC.

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Section: Discussionmentioning

confidence: 99%

Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis

Xie,

Li,

Tao

et al. 2024

J. Cancer

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“…In this study, we did not address dendritic cells such as macrophages. Tumorassociated macrophages (TAMs) are a diverse population of immune cells that play a complex role in CRC and probably in CAC prognosis [44]. Macrophages can polarize into M1 and M2 types, with distinct roles.…”

Section: Discussionmentioning

confidence: 99%

“…The type and location of TAMs can have different prognostic significance: M2 TAMs have been associated with poor CRC prognosis, and high M1 macrophage and CD68+TAM infiltration is correlated with a better prognostic situation in CRC patients [45]. The transition from UC to CAC involves two key processes, namely inflammation and tumorigenesis, both of which involve macrophages [44]. For example, in the UC inflammatory phase, excessive macrophage infiltration could worsen the inflammation by inducing proinflammatory cytokine production and promoting CAC.…”

Section: Discussionmentioning

confidence: 99%

“…Then, before tumor formation, M1 primarily drives inflammation and tumorigenesis. In established CAC, M1 inhibits progression via antitumor immunity, while M2 promotes tumor growth and metastasis [44]. Notably, some studies suggest that M2 not only advances tumors but also raises CAC risk, possibly due to its early-stage tumor-promoting role [46].…”

Section: Discussionmentioning

confidence: 99%

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Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer

Schardey,

Lu,

Neumann

et al. 2023

Cancers

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Background: Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. Methods: We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. Results: CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p = 0.02) and paracancerous tissues (p < 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p = 0.01), FOXP3+ regulatory T-cells (p < 0.01), and CD20+ B-cells (p < 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p < 0.01) and CD20+ (p < 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p < 0.038) and reduced CD8+ infiltrates (p = 0.02). Conclusion: In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.

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“…Macrophage polarization refers to the dynamic process by which macrophages transition into activated states under specific conditions ( Murray, 2017 ). In normal physiological circumstances, intestinal macrophages phagocytose microorganisms and initiate a controlled immune response as antigen-presenting cells ( Zhang et al, 2023 ). However, persistent and excessive inflammatory stimuli can lead to macrophage overactivation, which may damage the intestinal mucosa.…”

Section: Introductionmentioning

confidence: 99%

Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway

Gao,

Zhu,

Shuai

et al. 2024

Front. Pharmacol.

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Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD’s inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

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Roles of macrophages on ulcerative colitis and colitis-associated colorectal cancer

Cited by 33 publications

References 130 publications

Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis

Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis

Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer

Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway

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