A5103082558- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Lung Cancer Treatments and Mutations
- Inflammatory mediators and NSAID effects
- RNA modifications and cancer
- Lung Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Immune cells in cancer
- Chemokine receptors and signaling
- Ferroptosis and cancer prognosis
- Medical Imaging and Pathology Studies
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Fibroblast Growth Factor Research
- MicroRNA in disease regulation
APLA Health
2014-2025
VA Greater Los Angeles Healthcare System
2015-2024
University of California, Los Angeles
2015-2024
UCLA Jonsson Comprehensive Cancer Center
2014-2024
Howard Hughes Medical Institute
2014-2024
UCLA Health
2004-2023
University of Colorado Cancer Center
2000-2022
University of Colorado Denver
2000-2022
California NanoSystems Institute
2011-2021
Collaborative Research Group
2021
Myeloid suppressor cells (MSCs) producing high levels of arginase I block T cell function by depleting l-arginine in cancer, chronic infections, and trauma patients. In MSCs infiltrating tumors circulation are an important mechanism for tumor evasion impair the therapeutic potential cancer immunotherapies. However, mechanisms that induce unknown. Using 3LL mouse lung carcinoma, we aimed to characterize these mechanisms. Arginase expression was independent cell–produced cytokines. Instead,...
Abstract Naturally occurring CD4+CD25+ regulatory T cells (T reg) are pivotal in suppressing immune responses and maintaining tolerance. The identification of molecules controlling reg differentiation function is important understanding host malignancy autoimmunity. In this study we show that PGE2 enhances the vitro inhibitory human purified cells. Moreover, induces a phenotype CD4+CD25− PGE2-treated cell-mediated inhibition anti-CD3-stimulated lymphocyte proliferation did not require cell...
Abstract Cyclooxygenase (COX)-2 and its product prostaglandin (PG) E2 underlie an immunosuppressive network that is important in the pathogenesis of non–small cell lung cancer. CD4+CD25+ T regulatory (Treg) cells play role maintenance immunologic self-tolerance. Treg activities increase cancer appear to a suppressing antitumor immune responses. Definition pathways controlling will enhance our understanding limitation host Tumor-derived COX-2/PGE2 induced expression cell-specific...
Abstract Cyclooxygenase-2 (COX-2), the enzyme at rate-limiting step of prostanoid production, has been found to be overexpressed in human lung cancer. To evaluate tumor COX-2 modulation antitumor immunity, we studied effect specific genetic or pharmacological inhibition a murine Lewis carcinoma (3LL) model. Inhibition led marked lymphocytic infiltration and reduced growth. Treatment mice with anti-PGE2 mAb replicated growth reduction seen tumor-bearing treated inhibitors. was accompanied by...
We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only presence but also location tumors. CancerLocator simultaneously infers proportions and tissue-of-origin tumor-derived in blood sample using genome-wide methylation data. outperforms two established multi-class classification methods on simulations real data, even with low proportion scenarios. achieves promising results patient plasma samples sequencing coverage.
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung (NSCLC) accounting for over 85% all cases. Until recently, chemotherapy - characterized by some benefit but only rare durable responses was treatment option patients NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly and represent advent a new approach NSCLC. Three inhibitors, pembrolizumab, nivolumab atezolizumab, are now...
The National COVID Cohort Collaborative (N3C) is a centralized, harmonized, high-granularity electronic health record repository that the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools inform clinical care policy.
Abstract Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non–small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety tumor antigen–specific situ vaccination (ClinicalTrials.gov: NCT01574222). Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received...
The COVID-19 pandemic has had disproportionate effects on racial and ethnic minority communities, where preexisting clinical social conditions amplify health disparities. Many of these communities report lower vaccine confidence receipt the vaccine. Understanding factors that influence multifaceted decision-making process for uptake is critical narrowing COVID-19-related
Abstract Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they poorly characterized. We performed paired single-cell RNA B-cell receptor (BCR) sequencing of 16 early-stage LUADs 47 matching multiregion normal tissues. By integrative analysis ∼50,000 TIBs, we define 12 TIB subsets the LUAD adjacent ecosystems demonstrate extensive remodeling TIBs LUADs. Memory (PC) were highly enriched tumor tissues with more differentiated states increased...
Abstract Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells 1 . The mitochondria form highly organized networks, which their outer inner membrane structures define bioenergetic capacity 2,3 However, vivo studies delineating relationship between structural organization mitochondrial networks activity have been limited. Here we present an functional analysis phenotypes non-small cell lung (NSCLC) using integrated platform consisting positron emission...
Abstract Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies 1 . Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal samples. Epithelial comprised diverse cancer cell states, diversity among was strongly linked LUAD-specific oncogenic drivers. KRAS mutant showed distinct transcriptional features, reduced differentiation low levels of aneuploidy. Non-malignant...
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T recruitment ICB resistance. We evaluate intratumoral (IT) vaccination CXCL9- CXCL10-engineered dendritic cells (CXCL9/10-DC) as strategy overcome IT CXCL9/10-DC leads enhanced...
Cytokines play a vital role in the host immune response by regulating development and function of immunocompetent cells. To explore possibility that tumors may alter via release immunomodulatory cytokines, we studied two different skin cancers, basal cell carcinoma (BCC) squamous (SCC) as models. By RT-PCR, found type 2 IL-4 IL-10, were strongly expressed BCC compared with matched PBMC. Furthermore, IL-10 was more SCC benign growths. identify types responsible for production these tumor...
Elevated tumor cyclooxygenase-2 (COX-2) expression is associated with invasion, metastasis, and poor prognosis in non-small cell lung cancer (NSCLC). Here, we report that COX-2-dependent pathways contribute to the modulation of E-cadherin NSCLC. First, whereas genetically modified COX-2-sense (COX-2-S) NSCLC cells expressed low showed diminished capacity for cellular aggregation, genetic or pharmacologic inhibition COX-2 led increased resulted augmented homotypic aggregation among vitro. An...
Interleukin (IL)-10 is a pleiotropic cytokine which inhibits broad array of immune parameters including T helper cell type 1 (Th1) production, antigen presentation, and antigenspecific proliferation. To understand the consequences altered expression IL-10 in models autoimmune disease, response to infectious agents, tumors, we developed transgenic mice expressing under control IL-2 promoter. Upon vitro stimulation, spleen cells from unimmunized secrete higher levels lower amounts IFN-γ than...
Tumor cyclooxygenase-2 (COX-2) expression is known to be associated with enhanced tumor invasiveness. In the present study, we evaluated importance of COX-2 product prostaglandin E2 (PGE2) and its signaling through EP4 receptor in mediating non-small cell lung cancer (NSCLC) Genetic inhibition led diminished matrix metalloproteinase (MMP)-2, CD44, invasion. Treatment NSCLC cells exogenous 16,16-dimethylprostaglandin significantly increased receptor, MMP-2 matrigel contrast, anti-PGE2...
Abstract In this study, we show that Δ-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. two different weakly immunogenic murine cancer models, intermittent administration THC (5 mg/kg, four times/wk i.p. for 4 wk) led to accelerated growth tumor implants compared with treatment diluent alone. contrast our findings in immunocompetent mice, did not affect tumor-bearing SCID mice. The inhibitory cytokines, IL-10...
Abstract We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced cell-derived on antitumor immunity vivo, we utilized transgenic mice expressing under control IL-2 promoter. shown Lewis carcinoma cells (3LL) more aggressive growth potential compared with littermates. In this study, show transfer from to littermates transferred immunosuppressive effect and led 3LL tumor growth. addition changes cell-mediated...
Abstract Tumors produce a number of immunosuppressive factors that block the maturation CD34+ stem cells into dendritic (DC). We hypothesized tumors might also interfere with and/or function human monocyte-derived DC. In contrast to cells, we found CD14+ responded tumor culture supernatant (TSN) by increasing expression APC surface markers, up-regulating nuclear translocation RelB, and developing allostimulatory activity. Although displaying these characteristics mature DC, TSN-exposed DC...
Elevated tumor cyclooxygenase (COX-2) expression is associated with increased angiogenesis, invasion, and suppression of host immunity. We have previously shown that genetic inhibition COX-2 reverses the immunosuppression induced by non-small cell lung cancer (NSCLC). To assess impact in invasiveness, NSCLC lines were transduced a retroviral vector expressing human cDNA sense (COX-2-S) antisense (COX-2-AS) orientations. COX-2-S clones expressed significantly more protein, produced 10-fold...
Use of marijuana and cocaine is on the rise in United States. Although pulmonary toxicity from these drugs has occasionally been reported, little known about their effects lung microenvironment. We evaluated function alveolar macrophages (AMs) recovered lungs nonsmokers habitual smokers either tobacco, marijuana, or crack cocaine. AMs were deficient ability to phagocytose Staphylococcus aureus (p < 0.01). users also severely limited kill both bacteria tumor cells Studies using N...