Publications by authors named "Jiaji Yu"

7 Publications

  • Page 1 of 1

A neutral polysaccharide from restrains cisplatin-induced nephrotoxicity.

Food Sci Nutr 2021 Jul 11;9(7):3602-3616. Epub 2021 May 11.

Yunnan Provincial Key Laboratory of Panax notoginseng Faculty of Life Science and Technology Kunming University of Science and Technology Kunming China.

is an edible mushroom distributed over the south-eastern part of the Tibet Plateau, which is also recognized as an effective ethnomedicine to alleviate diseases. This study explored the effects of a kind of neutral polysaccharide (ONP) on RAW264.7 macrophages and cisplatin-induced nephrotoxicity. The results showed that ONP relieved the inflammatory response of RAW264.7 macrophages by increasing the expression level of anti-inflammatory factor IL-10. Furthermore, ONP treatment significantly prolonged the survival of the mice treated by cisplatin through decelerating pathological progress and alleviating damaged functions of the kidneys. Compared with the cisplatin group, ONP reduced the oxidative stress of the renal cells and the expression levels of pro-inflammatory factors. Apoptosis of renal cells was also weakened in the ONP treatment group. These findings indicated that ONP alleviated cisplatin nephrotoxicity mainly by inhibiting oxidative stress, inflammation, and apoptosis in the kidneys, underscoring the potential of ONP supplementation to alleviate the side effects of cisplatin chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.2317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269674PMC
July 2021

Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy.

Nat Commun 2021 06 10;12(1):3530. Epub 2021 Jun 10.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.

Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intratumoral MAOA expression with poor patient survival in a broad range of cancers. We further demonstrate that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192781PMC
June 2021

Targeting monoamine oxidase A for T cell-based cancer immunotherapy.

Sci Immunol 2021 May;6(59)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.

Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain, where it breaks down neurotransmitters and thereby influences mood and behavior. Small-molecule MAO inhibitors (MAOIs) have been developed and are clinically used for treating depression and other neurological disorders. However, the involvement of MAO-A in antitumor immunity has not been reported. Here, we observed induction of the gene in tumor-infiltrating immune cells. knockout mice exhibited enhanced antitumor T cell immunity and suppressed tumor growth. MAOI treatment significantly suppressed tumor growth in preclinical mouse syngeneic and human xenograft tumor models in a T cell-dependent manner. Combining MAOI and anti-PD-1 treatments generated synergistic tumor suppression effects. Clinical data correlation studies associated intratumoral expression with T cell dysfunction and decreased patient survival in a broad range of cancers. We further demonstrated that MAO-A restrains antitumor T cell immunity through controlling intratumoral T cell autocrine serotonin signaling. Together, these data identify MAO-A as an immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciimmunol.abh2383DOI Listing
May 2021

Ophiocordyceps lanpingensis polysaccharides attenuate pulmonary fibrosis in mice.

Biomed Pharmacother 2020 Jun 4;126:110058. Epub 2020 Mar 4.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with growing prevalence. Currently available therapies for treating IPF are not desirable due to the limited efficacy and multiple side effects. Ophiocordyceps lanpingensis is one strain of entomogenous fungi, which has been collected from the eastern part of the Himalayas. This study revealed that O. lanpingensis polysaccharides (OLP) could attenuate bleomycin (BLM) induced lung fibrosis in mice. Results showed that OLP treatments significantly reduced BLM-induced collagen deposition and decreased the accumulation of macrophages. The oxidative stress of the lung was alleviated by OLP. The expression levels of pro-inflammatory and pro-fibrogenic factors in OLP groups were also decreased compared with those in the BLM group, which might explain the improved alveolar integrity and function in the OLP treated groups. Our findings indicated that OLP treatment could alleviate pulmonary fibrosis progression mainly through reducing the recruitment of macrophages to the lungs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2020.110058DOI Listing
June 2020

Creatine uptake regulates CD8 T cell antitumor immunity.

J Exp Med 2019 12 18;216(12):2869-2882. Epub 2019 Oct 18.

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA

T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a () gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a "molecular battery" conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20182044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888972PMC
December 2019

Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.

Cell Stem Cell 2019 10 5;25(4):542-557.e9. Epub 2019 Sep 5.

Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; School of Nursing, University of California, Los Angeles, Los Angeles, CA 90095, USA; AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.stem.2019.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018522PMC
October 2019

Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules.

Proc Natl Acad Sci U S A 2018 11 22;115(45):E10702-E10711. Epub 2018 Oct 22.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;

Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2-restricted TCRs, limiting this approach to those patients expressing this allele. For these patients, TCR gene therapy trials have resulted in both tantalizing successes and lethal adverse events, underscoring the need for careful selection of antigenic targets. Broad and safe application of public antigen-targeted TCR gene therapies will require () selecting public antigens that are highly tumor-specific and () targeting multiple epitopes derived from these antigens by obtaining an assortment of TCRs restricted by multiple common MHC alleles. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we pilot an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1810653115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233129PMC
November 2018