Cellular metabolism of tumor‐associated macrophages – functional impact and consequences

Rabold, Katrin; Netea, Mihai G.; Adema, Gosse J.; Netea‐Maier, Romana T.

doi:10.1002/1873-3468.12771

Cited by 53 publications

(45 citation statements)

References 170 publications

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“…In the present study, we found that IDO1 expression was positively correlated with the expression of the inhibitory checkpoint molecules PD-L1, PD-L2, PD-1, and CTLA-4, as well as the infiltration of suppressive immune cells, including Tregs, TAMs, and MDSCs, in agreement with previous reports in various solid tumors [29][30][31][32][33][34]. Unexpectedly, the upregulation of IDO1 expression was positively correlated with an increased density of CD8 + TILs in PSCC, which may be related to a poor prognosis.…”

Section: Discussionsupporting

confidence: 93%

Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Zhou

Han

et al. 2020

Cancer Communications

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Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 up‐regulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008 and 0.032, respectively). High expression level of IDO1 in cancer cells and serum KTR were associated with short disease‐specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926; 95% confidence interval [CI], 2.458‐19.068; P < 0.001) and pathologic grade (HR, 2.194; 95% CI, 1.021‐4.529; P = 0.038), only serum KTR (HR, 2.780; 95% CI, 1.066‐7.215; P = 0.036) was an independent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon‐γ (IFNγ, P < 0.001) and immunosuppressive markers (programmed cell death protein 1, cytotoxic T‐lymphocyte‐associated protein 4 and programmed death‐ligand 1 and 2; all P < 0.05), and the infiltration of immune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells; all P < 0.001) in PSCC tissues. Furthermore, the expression of IDO1 was induced by IFNγ in a dose‐dependent manner in PSCC cells. Conclusions IFNγ‐induced IDO1 plays a crucial role in immunoediting and immunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1 catabolic activity, can be utilized as an independent prognostic factor for PSCC.

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Section: Discussionsupporting

confidence: 93%

Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Zhou

Han

et al. 2020

Cancer Communications

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“…Cytokines such as IL-6 and tumour necrosis factor (TNF) that are produced by trained cells are associated with increased tumorigenicity and the spread of metastases in specific types of tumours, including oral squamous cell carcinoma and lung, kidney and breast cancer 164,165 . Cancer cells also produce a series of soluble mediators that can induce direct epigenetic and metabolic reprogramming in immune cells and can thereby contribute to the progression of the tumour 166 .…”

Section: Trained Immunity and Neurodegenerative Diseasesmentioning

confidence: 99%

Defining trained immunity and its role in health and disease

et al. 2020

Self Cite

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| Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity. ✉

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“…In general, studies have indicated that the presence of macrophages within the tumor microenvironment (i.e., TAMs) was associated with poor prognosis in cancer patients [223,224]. Often TAMs display M2 phenotype [225–227].…”

Section: Leptin In Tumor Progressionmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

100

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The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

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Cellular metabolism of tumor‐associated macrophages – functional impact and consequences

Cited by 53 publications

References 170 publications

Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Defining trained immunity and its role in health and disease

The potential role of leptin in tumor invasion and metastasis

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