A5008219651- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Immune cells in cancer
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Renal cell carcinoma treatment
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- CAR-T cell therapy research
- interferon and immune responses
- Prostate Cancer Treatment and Research
- Acute Myeloid Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- Psoriasis: Treatment and Pathogenesis
- Cancer-related molecular mechanisms research
City Of Hope National Medical Center
2015-2025
City of Hope
2016-2025
Beckman Research Institute
2015-2025
University of Southern California
2022
University of California, Los Angeles
2022
Therapeutics Clinical Research
2022
Data Harbor (United States)
2015
Oncotherapeutics (United States)
2015
Poznan University of Medical Sciences
2013
Institut de Recherche Vaccinale
2013
Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role cancer remains to be further explored. IL-17 has been shown elevated several types of cancer, but how it might contribute tumor growth is still unclear. We show that B16 melanoma MB49 bladder carcinoma reduced IL-17−/− mice drastically accelerated IFN-γ−/− mice, contributed by intratumoral IL-17, indicating a promoting growth. Adoptive transfer studies...
Abstract STAT3 activation has been observed in several autoimmune diseases, suggesting that STAT3-mediated pathways promote pathologic immune responses. We provide vivo evidence the fundamental role of signaling autoimmunity relates to its absolute requirement for generating TH17 T cell show is a master regulator this pathogenic subtype, acting at multiple levels vivo, including differentiation and cytokine production, as well induction RORγt IL-23R. Neither naturally occurring cells nor...
The underlying molecular mechanisms that cause immune cells, mediators of our defense system, to promote tumor invasion and angiogenesis remain incompletely understood. Constitutively activated Stat3 in cells has been shown angiogenesis. Therefore, we sought determine whether activation tumor-associated inflammatory a similar function. We found signaling mediates multidirectional crosstalk among myeloid the stroma, ECs contributes mice. Myeloid-derived suppressor macrophages isolated from...
Growing evidence links tumor progression with chronic inflammatory processes and dysregulated activity of various immune cells. In this study, we demonstrate that types macrophages internalize microvesicles, called exosomes, secreted by breast cancer non-cancerous cell lines. Although both exosomes targeted macrophages, only cancer-derived stimulated NF-κB activation in resulting secretion pro-inflammatory cytokines such as IL-6, TNFα, GCSF CCL2. vivo mouse experiments confirmed...
Abstract Previous studies have suggested that the gut microbiome influences response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product we postulated could augment CPI through modulation of microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive metastatic renal cell carcinoma clear and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 receive nivolumab ipilimumab without...
Supplementation with CBM588, a bifidogenic live bacterial product, has been associated improved clinical outcomes in persons metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants locally advanced or mRCC histological confirmation of clear cell, papillary sarcomatoid component were randomized 2:1...
Abstract As the main effector‐cell population of central nervous system, microglia (MG) are considered to play an important immunoregulatory function in a number pathological conditions such as inflammation, trauma, degenerative disease, and brain tumors. Recent studies, however, have suggested that anti‐neoplastic MG may be suppressed malignant Considering proposed suppressive role signal transducers activators transcription 3 (Stat3) antitumor immunity, we evaluated Stat3 inhibition on...
Hypoxia-inducible factor 1 (HIF-1) is a potent tumorigenic factor. Its alpha subunit (HIF-1alpha), which tightly regulated in normal tissues, elevated tumors due to hypoxia and overactive growth signaling pathways. Although much known about HIF-1alpha regulation cancer cells, crucial molecular targets that affect levels modulated by both oncogenic pathways remain be identified. Additionally, whether how the tumor microenvironment contributes accumulation unclear. This study shows novel...
Recent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived suppressor cells (MDSC) are important inhibitors T-cell responses solid tumors, such as prostate cancers. However, targeting MDSCs proved challenging due their phenotypic heterogeneity.Myeloid cell populations were evaluated using flow cytometry on blood samples, functional assays, immunohistochemical/immunofluorescent stainings specimens from...
Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type IFN not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival leukemia-bearing diminished the absence signaling, suggesting STING may be triggered AML. However, agonist, DMXAA, induces expression IFN-β and other inflammatory cytokines, promotes dendritic (DC) maturation, results...
Intracellular therapeutic targets that define tumor immunosuppression in both cells and T remain intractable. Here, we have shown administration of a covalently linked siRNA to an aptamer (apt) selectively binds cytotoxic lymphocyte–associated antigen 4 (CTLA4apt) allows gene silencing exhausted CD8+ Tregs tumors as well CTLA4-expressing malignant cells. CTLA4 expression was upregulated the milieu; therefore, CTLA4apt fused STAT3-targeting (CTLA4apt–STAT3 siRNA) resulted internalization into...
Abstract Improving effector T-cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Signal transducer and activator transcription 3 (Stat3) in the myeloid compartment constrains Th1-type immunity, dampening natural induced antitumor immune responses. We have recently developed an vivo small interfering RNA (siRNA) delivery platform by conjugating a Toll-like receptor 9 agonist with siRNA that efficiently targets B cells. Here, we show either CpG...