IL6 elevation

Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Our study suggests that low levels of IFN-γ before immune checkpoint inhibitor treatment may be useful for the detection of a poor immunological status. Hence, a reduction in IL-6 levels is predictive of a longer PFS, and increased IL-4 levels are predictive of a good response. IL-4 and IL-6 may, therefore, serve as promising circulating predictive biomarkers for patients who can benefit from anti-PD-1 monoclonal antibodies administered in combination with chemotherapy.

High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment.

High IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production from CD8+ T cells. Overall, high baseline serum IL-6 levels were associated with worse survival outcomes and reduced T-cell responses in Pembro/Axi-treated advanced RCC patients.

Globally, our results establish MTX as a macrophage reprogramming drug and indicate that its ability to modulate macrophage polarization may also underlie its therapeutic benefits. Since GSK3β inhibition abrogates the reprogramming action of MTX, our results suggest that the GSK3β-MAFB/MAF axis constitutes a target for the macrophage-centered antitumor strategies.

Recently atezolizumab/bevacizumab (Atezo/Bev) combination chemotherapy regimen became the first line therapy of advanced HCC. Circulating IL-6 levels may be a novel prognostic biomarker for advanced HCC patients who underwent combination immunotherapy.

Background Combination anti-PD-1 (Nivolumab) and anti-CTLA-4 (Ipilimumab) have improved objective response rates and overall survival in patients with renal cell carcinoma (RCC) over Sunitinib. indicate that novel immunotherapeutic strategy utilizing oligonucleotide-based STAT3 inhibitor (CpG-STAT3ASO) targeting myeloid cells with anti-PD-1 can achieve significant tumor growth inhibition and warrant further investigation into myeloid cell targeting with anti-PD-1 therapy in RCC. Keywords: Nivolumab, Ipilimumab, RCC, STAT3, myeloid cells, immunosuppression

A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. No abstract available

Our findings provide cellular and molecular mechanisms for the pro-tumorigenic functions of MUC1 in the inflamed colon. Therapeutic strategies to inhibit MUC1 signal transduction warrant consideration for the prevention or therapy of CAC.

In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.

The model combining IL-6 with CRP levels helped predict the outcomes of mPC patients treated with mFOLFIRINOX (AUC: 0.811, 95%CI: 0.639-0.983, P=0.003). The serum levels of IL-6 and CRP might be considered as valuable biomarkers in predicting the outcomes of patients with mPC who received the mFOLFIRINOX regimen.

Higher IL-6 and CRP levels in patients with advanced PDAC suggest an important role of these inflammatory markers in tumour progression. Furthermore, the association of mutations in the K-ras gene with serum IL-6 indicates cross-talks that may contribute to the progression of the PDAC.

We confirmed that IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway, which might be the therapeutic targets for OSCC remedy.

In conclusion, IL-6 promotes chemoresistance in AML through the stat3/CD36-mediated FA uptake. Blockade of CD36 improved the effect of Ara-c, representing a promising strategy for AML therapy.

This process could neither be prevented by iron nor erythropoietin (EPO) treatment. Trp53floxWapCre mice are the first mouse model where EPO-resistant anemia is described and may serve as a disease model to test therapeutic approaches for a subpopulation of human cancer patients with normal or corrected iron levels that do not respond to EPO.

In vivo, this combination inhibits tumor growth of xenografts bearing osimertinib-resistant tumors. Taken together, we conclude that Laminin α5/FAK signaling is responsible for IL-6-induced osimertinib resistance, which could be reversed by combination of ibrutinib and osimertinib.

TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.

Atezolizumab/bevacizumab (Atezo/Bev) combination therapy has become a front-line therapy for advanced hepatocellular carcinoma (HCC), but approximately 20% of patients are nonresponders. Multivariate Cox proportional hazards analysis showed that IL-6 level and age were independent risk factors for disease progression (hazard ratio of 2.785 and p = 0.015 for IL-6, and hazard ratio 0.306 and p = 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.

Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response. Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.

Our results suggested a possible association of IL-6-174 GG with CaCx, which was also associated with high IL-6 levels. Decreased levels of IL-6 following treatment indicate its possible prognostic use in CaCx cases.

Jain, et al; Blood 2019; 134 (Supplement_1): 2885. doi: https://doi.org/10.1182/blood-2019-131041

Our study suggests a potential association between epigenetic regulation of inflammatory mediators in VAT - such as IL6 - in the CRC context, in which 25(OH)D may mediate this risk. Therefore, vitamin D could affect the epigenetic status of IL6, which can be considered for additional preventive strategies.

In RAPN, the retroperitoneal approach was linked to a risk for increased postoperative serum levels of inflammatory cytokines. The serum level of IL-6 at POD1 was associated with postoperative renal deterioration in patients with RCC treated with RAPN.

Increase in IL-6, IL-10, NLR, PLR, and LDH levels or reduced ALC and ALB levels were associated with the occurrence of CIP in lung cancer patients. High IL-6 and low ALB levels at onset of CIP were related to severe grade and poor prognosis of CIP.

It was notable that indicator composed of IL-6 and neutrophils/lymphocytes ratio (NLR) occupied the superior position of Area Under Curve (AUC) values in cancer cases, especially in patients with solid tumors (AUC = 0.85). The newly-found indicator could also be referred as an independent risk factor, which provided us with novel clues on the investigation of more reliable and affordable clinical indexes in tumor prediction.

We hypothesize that high IL-6 levels due to Stauffer's syndrome might have contributed to immune-related hepatic failure. Consider Stauffer's syndrome in patients who develop liver toxicity unresponsive to immunotherapy.Evaluate IL-6 as high levels are seen in Stauffer's syndrome patients undergoing immunotherapy.Consider taking a liver biopsy to assess the severity of liver injury.