IDO1 expression

Treatment with the KRasG12C-specific inhibitor, ARS-1620, significantly increased IDO1 expression, which inversely correlated with PD-L1 expression in the KRasG12C-mutant H358 cell line...Moreover, the induction of IDO1 expression following KRas inhibition appears to operate independently of the MAPK pathway. Our results propose that concurrent targeting of KRas and IDO1 could potentiate therapeutic efficacy in KRas-mutant cancers, overcoming resistance to immune checkpoint blockade.

IDO1 promoter methylation and expression are associated with prognosis, immune cell infiltration, immune-related pathways, and immunomodulator expression in breast cancer. Our findings provide evidence for the validation of IDO1 promoter methylation as a promising biomarker to predict responses to immune checkpoint inhibitors in patients with breast cancer.

N-3 PUFA deprivation reduced NA content and increased the indoleamine 2,3-dioxygenase-1 expression in females, while acetylcholine and tumor necrosis factor alpha were higher in males. Taken together, our data indicated that deficiency of n-3 PUFA in diet induced mood disorders in adolescent animals, however this behavioral phenotype is accompanied by a different immune activation in male and female rats.

While higher IDO1 expression is associated with the risk of advanced tumor stage in HNSCC, its impact on overall and progression-free survival remains inconclusive. Further research is needed to elucidate its prognostic significance and therapeutic potential.

Vitamin D3 ameliorated intestinal damage in neonatal rats with NEC and exerted antiinflammatory and immunomodulatory effects on DCs. Vitamin D3 has potential as a supplementary treatment for NEC patients.

IDO1 expression in a total of 102 tissues with tumor and tumor microenvironment was detected by quantitative PCR (q-PCR). In gastric tumors, 3,25-fold decreased expression of IDO1 was detected according to the tumor microenvironment (p=0,05), IDO1 expression was found to be more than 2 times higher in signet ring cell carcinoma (SRCC) and poorly differentiated tumors without distant organ metastasis (p<0,05), In GC, tryptophan level was found to be 1,6 times lower than in control (AUC:0889; cut off≤21,57; p<0001), Low tryptophan level was found in advanced tumor stage compared to early stage and in the presence of perineural invasion compared to its absence (p<0,05) The level of kynurenine was found to be approximately 1,8 times lower in SRCC (p=0,04), Increased tryptophan accumulation in the gastric tumor and its microenvironment, when catabolized via IDO1, exhibits histological type, tumor differentiation, and metastasis-promoting effects more prominently in aggressive subtypes such as SRCC.

Mechanistically, the kynurenine released from IDO1-expressing CRC cells inhibited the IGFBP5/p53 signaling pathway, accounting for IDO1-mediated suppression of cell senescence and induction of chemoresistance. Collectively, these data revealed an unrecognized role of IDO1 in senescence escape and chemoresistance via releasing its catabolite kynurenine, implicating that therapeutically targeting IDO1 or IGFBP5/p53 signaling pathway holds great promise for CRC treatment.

Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8)...mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.

XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.

This study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy.

The results indicate that the expression of PD-L1 and IDO increases in OLP and OLL, suggesting that these molecules may play a role in the pathogenesis of both disorders.

Serum HMGB1 and IDO levels were significantly increased in ESCC patients, and with the progression of ESCC patients, serum HMGB1 and IDO levels were also gradually increased; serum HMGB1 was significantly correlated with IDO; serum HMGB1 and IDO combined with CEA and SCC-Ag were of high value in predicting the clinical progression of ESCC patients; the absolute counts of CD4+CD28+T cells and CD8+CD28+T cells in high HMGB1 group were significantly lower than those in low HMGB1 group, while the percentage of CD4+PD-1+T cells was significantly higher than that in low HMGB1 group; the percentage and absolute counts of CD4+CD28+T cells and the absolute counts of CD8+CD28+T cells in high IDO group were significantly lower than those in the low IDO group, while the percentage of CD8+PD-1+T cells was significantly higher than that in the low IDO group; increased serum HMGB1 and IDO expression levels were closely related to poor prognosis in ESCC patients; and HMGB1 may promote IDO expression by activating NF-κB signaling pathway. Serum HMGB1 and IDO have a synergistic effect, they inhibit immune function and promote tumor progression in ESCC patients, and also lead to poor prognosis.

The Cancer Imaging Archive data analysis revealed that the impact of anti-PD1 and CTLA4 therapy is more pronounced in cervical cancer patients exhibiting elevated IDO1 expression. IDO1 is a potential target for immunotherapy for cervical cancer.

Results suggest that R- and S-ketamine have pro-neurogenic and anti-inflammatory properties, however, this is mediated by inhibition of the kynurenine pathway only in the context of IL-1b. Overall, this study enhances our understanding of the mechanisms underlying ketamine's antidepressant effects in the context of different inflammatory phenotypes, ultimately leading to the development of more effective, personalised therapeutic approaches for patients suffering from depression.

Therefore, the data suggest that the GBM microenvironment controls tryptophan levels by regulating IDO-1 expression, which plays a critical role in immune suppression. These findings support the use of immune therapy in combination with IDO-1 inhibitors or tryptophan supplementation as a potential treatment strategy.

We show that IDO1 inhibition delays tumourigenesis in Dock2 knockout mice, and we confirm that this pathway is conserved across species as IDO1 expression is elevated in human IBD-CRC and in sporadic CRC cases with mutated DOCK2. Together, these data demonstrate a previously unidentified tumour suppressive role of DOCK2 that limits IFNγ-induced IDO1 expression and cancer progression, opening potential new avenues for therapeutic intervention.

Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.

NGS results highlighted underlying genetic heterogeneity within samples, which may have a confounding influence on the expression of a particular biomarker. T-TMAs, integrated with quantitative biomarker digital scoring, are useful tools to identify hallmark specific expression of biomarkers in pancreatic cancer.

Overall, our results suggest that IDO1 tryptophan metabolites produced by neuronal cells may act on AHR in pathogenic CD4+ T cells in a paracrine fashion in the CNS and that the specific induction of IDO1 expression in neurons at disease-afflicted sites can be considered a therapeutic approach to block the progression of multiple sclerosis without affecting systemic immunity.

We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy...In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

IDO1 expression is closely correlated with the immune profile of the HNSCC. This observation should be explored further to elucidate the potential of targeting IDO1 as a novel immunotherapeutic approach for HNSCC.

IDO1 inhibitors could inhibit glycolysis, promote apoptosis, and exhibit robust therapeutic efficacy when combined with GLUT1 inhibitor in PC mice. Our study reveals the function of IDO1 in the glucose metabolism of PC and provides new insights into the therapeutic strategy for PC.

These data show that analysis of CDK12 alteration, in the context of MHC expression levels, and LOH status may offer improved predictive value for outcomes in this potentially actionable genomic subgroup of PCa. In addition, these findings highlight the need to explore novel therapeutic strategies to enhance MHC expression in CDK12-defective PCa to improve immunotherapy responses.

Several iTMEs exist during tumor evolution and NACT impact on iTME is heterogeneous. Clustering analysis of patients, unravels several IC subsets within OC and can guide future personalized approaches. Targeting different checkpoints such as TIM-3, LAG-3 and IDO-1, more prevalent than PD-L1, could more effectively harness anti-tumor immunity in this anti-PD-L1 resistant malignancy.

In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.

Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival...Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

IDO1 expression warrants further exploration as a predictive biomarker for immunotherapy. Moreover, co-expressed immunoregulatory molecules merit exploration for co-targeting.

Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs. B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.

The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.

The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.

Their potential to deliver potent dual inhibition of IDO1/TDO2, along with safety and favorable pharmacokinetics, makes them compelling. Validation through in vitro and in vivo assays should be conducted to confirm their activity, selectivity, and preclinical potential as holo IDO1/TDO2 dual inhibitors.Communicated by Ramaswamy H. Sarma.

Together, our findings unveil a mechanism of mitophagy in OC angiogenesis and indicate the clinical relevance of EV enriched L-kyn as a potential biomarker for tumorigenesis and progression. Additionally, IDO1 inhibitors might become an alternative option for OC adjuvant therapy.

Lastly, IDO1 and PDL1-specific CD4+ T cell clones from melanoma patients treated with IO102-IO103 vaccine could selectively target cells differentially expressing IDO1 or PDL1.Our data collectively show that cells expressing IDO1 and PD-L1 represent distinct populations in the TME thus targetable by the IDO1-PD-L1 vaccination approach...These data are supported by ex vivo functional assays using target specific T cells from vaccinated patients. Altogether, our data support the use of a dual antigen approach to reduce the immunosuppression and enhance anti-tumor effect.

Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8+ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes.

The effects of calcitriol on breast CAFs, both at the gene and protein levels, are complex, reflecting the immunosuppressive or procancer properties of CAFs. The anticancer polarization of CAFs following ex vivo calcitriol treatment may result from decreased CCL2, TNC (gene and protein), MMP9, and MMP-2, while the opposite effect may result from increased PDPN, TIMP1 (gene and protein), and SPP1. Despite these multifaceted effects of calcitriol on molecule expression, CAFs' CMs from nonmetastatic and postmenopausal patients treated ex vivo with calcitriol decreased the migration of MCF-7 cells.

IDO1 was mainly expressed in monocytes and dendritic cells, and high IDO1 activity in monocytes was associated with enriched immunostimulatory pathways. Our findings provided in-depth information about the infiltration patterns and prognostic value of cells expressing IDO and/or ARG1 in the colorectal cancer microenvironment highlighting the significance of host immune response in tumor progression.

Overall, our findings unveiled a new mechanism of action of epacadostat on IDO1 target, repositioning the catalytic inhibitor as a stabilizer of the apo-form of IDO1, still capable of transducing a pro-tumorigenic pathway in SKOV-3 tumor. This mechanism could contribute to clarify the lack of effectiveness of epacadostat in clinical trials and shed light on innovative immunotherapeutic strategies to tackle IDO1 target.

In the following feature selection analyses, four metabolites, namely, cyclopentyl fentanyl-d5, LPI 17:0, guanosine-3',5'-cyclic monophosphate, kynurenine (KYN, high in EMPD) were identified by both random forest and support vector machine analyses...In conclusion, this study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD.

Consequently, these effects result in efficient immune infiltration and positive anti-tumor outcomes. In conclusion, the HBI NDs nanodrug exhibits considerable potential as a novel agent for enhancing anticancer efficacy and promoting immune infiltration.

Our data suggest that the detection of somatic mutations in DDR genes can predict the efficacy of immunotherapy in patients with ccRCC. Furthermore, we revealed the unique molecular and immune mechanisms underlying ccRCC with DDR gene mutations.