S100A8 expression

Notably, similar to CAFs, immunosuppressive tumor-associated macrophage (TAM) subtypes underwent glycolipid metabolism reprogramming via PPARgamma regulation, promoting tumor metastasis. These findings shed light on the mechanisms driving the aggressiveness of HGSC, offering crucial insights for the development of novel therapeutic targets against this formidable cancer.

Our study discovered that Sec C was a powerful anti-colorectal CSC agent, and that the positive feedback loop of p38-S100A8 mediated Sec C activity. This showed that Sec C could act as a promising clinical candidate in colorectal cancer treatment, and S100A8 could be a prospective drug target.

Our data propose S100A8/A9 as a potential predictive and pharmacodynamic biomarker in clinical trials evaluating combination therapy targeting PIM and immune checkpoints in TNBC. This work encourages the development of S100A8/A9-based liquid biopsy tests for treatment guidance.

Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.

Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.

These findings reveal a novel regulatory loop involving S100A8/A9 and miRNA-132-5p that modulates IL-8 secretion by neutrophils in inflammatory conditions. This loop could be a potential target for therapeutic intervention in inflammatory diseases.

These data improve our understanding about why some tumors with brisk tumor-infiltrating lymphocytes do not respond to immunotherapy and provide a compelling rationale to target myeloid checkpoints in MCC. See related article by Tabachnick-Cherny et al., p. xxxx.

Our data revealed a hereunto unrecognized therapeutic 'miR-17-20a-RCAN3' pathway in the ischemic vasculature that is VEGFR1-STAT3/S100A8/A9 independent and is activated only upon VEGFb-inhibition in PAD.

A recent report sheds light on the tumor-associated macrophages (TAMs) in MCC, and the association of S100A8-expressing TAMs with resistance to anti-PD-(L)1 inhibitors. These data improve our understanding about why some tumors with brisk TIL do not respond to immunotherapy and provide a compelling rationale to target myeloid checkpoints in MCC.

The S100A8/9-RAGE pathway and CD8 expression were increased in smoking-related NSCLC patients. The S100A8/9-RAGE pathway could be a promising biomarker for chronic airway inflammation and carcinogenesis in smoking-related lung diseases.

S100A8/A9 is remarkedly increased in basal-like and Her2-overexpressed subtypes, predicting poor prognosis of breast cancer patients. Tumor suppressor DACH1 inhibits S100A8/A9 expression. The combination of S100A8/A9 and DACH1 predicted the overall survival of breast cancer patients more preciously.

Following treatment with different concentrations of decitabine, the MDSCs cell count progressively decreased with increasing treatment time and concentration (Fig d)...This gene can induce neutrophil chemotaxis and adhesion, serving as a danger-associated molecular pattern (DAMP) molecule and stimulating innate immune cells through pattern recognition receptors (e. g. , TLR4 and AGER), subsequently activating MAP kinase and NF-kappa-B signaling pathways, leading to inflammation and fibrosis. Thus, it can be inferred that the number of MDSCs in myelofibrosis patients is negatively correlated with GPX1 gene expression and positively correlated with S100A8/S100A9 gene expression.

Furthermore, enforced expression of S100A9 in Jak2 mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2 and Jak2 mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice.

The present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis.

Triple-negative breast cancer, for example, has only one FDA-approved treatment for metastatic disease in the upfront setting, chemo plus Pembrolizumab...Our results indicate that soluble S100A4 protein promotes cancer-associated M-MDSC and PMN-MDSC/neutrophils frequencies in the peripheral blood and lung tissue, respectively, to prime the lung metastatic niche. Notably our anti-S100A4 monoclonal antibody has ~10-fold higher affinity for human S100A4 protein compared to mouse S100A4 protein, suggesting that it is a highly promising drug candidate for future clinical development.

Background: More than 95% of acute promyelocytic leukemia (APL) patients can achieve complete remission by dual induction of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Our data indicate that ATRA induction could overcome immune evasion through downregulating immune checkpoint molecules. ATRA-induced upregulation of S100A8/A9 may contribute to the cytokine storm observed in the DS stage of APL patients by activating the JAK-STAT and NF-κB signaling pathway. S100A8/A9 is recommended as a biomarker for predicting APL DS.

Venetoclax (anti-BCL2) is approved for elderly patients with acute myeloid leukemia (AML) in combination with hypomethylating agents such as azacitidine or decitabine. Our in vitro and in vivo results demonstrate that HC-7366 is a potent GCN2 activator with strong antitumor activity in AML as a single agent and in combination with venetoclax. The potential of HC-7366 to counteract multiple known resistance mechanisms to venetoclax could provide a viable treatment option for patients with relapsed/refractory AML when used in combination with venetoclax.

Therefore, the objective of this study is to investigate the function of S100A8 on proliferation in mammary epithelial cells after its deletion and to elucidate the underlying proteins involved in downstream signaling. Our findings indicate that the deletion of S100A8 leads to excessive proliferation in normal mammary epithelial cells, reduces apoptosis, and affects cell-cell adhesion molecules required for cellular communication, resulting in a cancer-like phenotype.

Our data confirm that S100A8/A9 hi AML blasts possess particular biological characteristics. Especially the prominent immune escape profile will be further investigated in functional assays taking into consideration the current development of novel immunotherapies (e.g., bispecific antibodies or CAR T cells) beyond allogeneic stem cell transplantation. Overall, S100A8/A9 hi AML blasts appear to be better protected not only from chemotherapy but also from immune responses.

6mo Helicobacter felis-infected S100a8Cxcr2 mice exhibited worsened gastric metaplastic pathology than Cxcr2 mice, which was associated with dysregulated lipid metabolism and peroxidation. S100a8 is a pan-specific marker that can be used to target gastric G-MDSC subpopulations, of which the Cxcr2 subset regulates gastric immunopathology and associates with the regulation of lipid peroxidation.

Overall, S100A8 knockdown restrained RCC malignant biological properties, which was associated with the deactivation of the NF-κB signaling pathway. This present study demonstrates new insights that S100A8 may be a potential therapeutic target in RCC.

We further revealed that SERPINB3 promoted STAT-dependent expression of chemokines, whereby inhibition of STAT activation by ruxolitinib or siRNA abrogated CXCL1/8 and S100A8/ A9 expression in SERPINB3 cells. Patients with elevated pre-treatment SCCA and high pSTAT3 had increased intratumoral CD11b+ myeloid cell compared to patients with low SCCA and pSTAT3 cohort that had overall improved survival after radiotherapy. These findings provide a preclinical rationale for targeting SERPINB3 in tumors to counteract the immunosuppression and improve response to radiation.

Amplification of S100A8 does not appear to be associated with S100A8 protein expression in breast cancer. S100A8 protein expression in tumor epithelial cells identifies a subgroup of predominantly non-luminal tumors with a high mean age at diagnosis and significantly worse prognosis. Finally, S100A8 alone is not a sufficient marker to identify infiltrating immune cells linked to worse prognosis.

Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia.

M1-polarized macrophages were the predominant cell type expressing S100A8 and S100A9 in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL6 to up-regulate S100A8 and S100A9 expression in macrophages of M1 type.

We demonstrated that combination therapy with divalent peptide3A5 and bevacizumab synergistically suppressed tumor growth in SW480 xenograft models...As most tumor cells including SW480 cells also express TLR4, S100A8 inhibitory peptides would target both the tumor microenvironment and tumor cells. Thus, multivalent S100A8 inhibitory peptides would provide new pharmaceutical options for aggressive cancers.

In HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy.

Despite this heterogeneity, in half our cohort, we identified a recurrent gene expression signature associated with immature immunophenotype, which correlated with genetic drivers of immunophenotype in some cases. Future multiomic studies are needed to completely subtype MPAL and elucidate the impact of these subtypes on treatment outcomes.

The possible mechanism involves promoting apoptosis through downregulation of S100A8 expression by inhibiting the PI3K/AKT signaling pathway. This study provides a potential treatment strategy and theoretical support for overcoming the clinical ABT-199 resistance problem in AML patients.

2 Our data suggests a correlation of S100A8-expressing cells in MCC tumors with response to treatment, as the ratio of S100A8-to-CD8 is higher in inflamed tumors that did not respond to immunotherapy. Future approaches to target M-MDSCs, or S100A8 directly might modify the ratio of S100A8-to-CD8 and potentially improve patient responses to PD-(L)1 blockade treatment.

We present a new translational strategy of EMCN as a new key player in tumor lung metastasis by affecting the host microenvironment. These findings could provide a sound theoretical basis for clinical treatment.

The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.

Moreover, IL-10 inhibited activation of NF-κB signaling (4-fold, p < 0.05). In conclusion, inflammation stimulated the S100A protein expression mediated via the proliferation-related signaling and balanced by the cytokines in CLL.

We identified ISLR as a potential biomarker for PRAD bone metastasis. Moreover, the genes identified to have prognostic value may act as therapeutic targets for PRAD bone metastasis.

S100A8 levels were compared in B-ALL and relapsed B-ALL lymphoblasts that were sensitive and resistant to Vincristine, respectively...According to the findings of the present study, S100A8 is effective in developing lymphoblast resistance to chemotherapy, and its enhanced expression may contribute to shifting B-ALL into the relapse phase of the illness. As a result, S100A8 may be a valuable target for managing and improving relapses B-ALL.

Ex-vivo treatment of splenocytes with S100A8 protein activated NK cells. Our results indicate that treatment with S100A8 may favourably modify the lung microenvironment to promote an effective immune response in lungs, thereby representing a new strategy that could complement current immunotherapies in lung cancer.

The present study provides novel mechanistic insights on RAGE actions in TNBC. Moreover, our findings suggest that RAGE-FAK-YAP transduction pathway could be exploited as a druggable system halting the aggressive TNBC subtype.

In summary, normal SC and the novel luminal progenitor cell population likely give rise to basal-like and HER2-overexpressing BrCs, respectively. Characterizing these normal cell populations may facilitate a better understanding of specific BrCs subtypes.

We could identify stromal cell-derived interleukin-6 (IL-6) as the trigger for a Jak/STAT3 signaling-mediated S100A8/A9 induction. Interfering with fatty acid uptake and the IL-6-Jak/STAT3 pathway antagonized formation of S100A8/A9high cells and therapeutic resistance, which could have therapeutic implications as a strategy to interfere with the AML-niche dynamics.