About

Lili Yang is a professor in the Department of Microbiology, Immunology and Molecular Genetics (MIMG) at UCLA Samueli School of Engineering. Her research interests include off-the-shelf immune cell therapy, stem cell engineering, cancer immunotherapy, autoimmunity, infections, and CAR-NKT/rdT/MAIT. She holds a B.S. in Biology from the University of Science & Technology of China, an M.S. in Biomedical Sciences from the University of California, Riverside, and a Ph.D. in Biology from the California Institute of Technology, where she was mentored by David Baltimore. Her notable contributions focus on advancing immune cell therapies and engineering approaches to treat cancer and immune-related diseases.

Research topics

• Biology
• Cancer research
• Internal medicine
• Immunology
• Biochemistry
• Medicine
• Materials science
• Chemistry
• Cell biology
• Biophysics
• Nanotechnology
• Pharmacology
• Photochemistry

Selected publications

• A proposal to simplify the definition of metabolic dysfunction-associated steatotic liver disease in youths

  HepatoBiliary Surgery and Nutrition · 2026-01-21

  articleOpen access1st authorCorresponding
  PublisherDOI

• Redefining multiple sclerosis with CAR-T cell therapy

  Molecular Therapy · 2025-12-11

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells

  Cell Reports Medicine · 2025-08-29 · 11 citations

  articleOpen accessSenior author

  Li et al. generate allogeneic CD70-directed CAR-engineered NKT (AlloCAR70-NKT) cells from hematopoietic stem and progenitor cells using a clinically guided culture method. These cells exhibit multimodal targeting of renal cell carcinoma (RCC) tumor cells, the tumor microenvironment, and alloreactive T cells, representing a promising approach for metastatic RCC therapy.

  PublisherOA PDFDOI

• Indoleamine 2,3-dioxygenase 1 alters the proportions of B cell subpopulations in the microenvironment of acute myeloid leukemia

  Molecular Biomedicine · 2025-04-16 · 3 citations

  articleOpen access

  Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients' bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.

  PublisherOA PDFDOI

• A Nanovial-Based Platform for Functional Discovery of Antigen-Reactive TCRs from Unconventional T Cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-07

  preprintOpen accessCorresponding

  Abstract Unconventional T cells, such as mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells, recognize non-peptide antigens presented by MR1 and CD1d, respectively, and play pivotal roles in immunity, allowing targeting of cells based on metabolic activity. Although components of the T cell receptors (TCRs) for these unconventional T cells are invariant, significant variability in the CDR3 regions still exist, opening questions as to how TCR sequence and function may be linked, and how to maximize the therapeutic potential of engineered unconventional T cells. Here, we develop a nanovial-based functional screening platform that enables high-throughput discovery of TCRs from unconventional T cells based on direct antigen recognition and cytokine secretion. By selectively labeling nanovials with MR1 and CD1d molecules displaying their cognate ligands, we achieve dose-dependent capture and activation of MAIT and iNKT cells from complex human PBMC samples comprising tens of millions of cells. Using oligonucleotide barcodes conjugated to nanovials encoding the antigen-presenting molecules and loading cytokine capture antibodies, we perform secretion-encoded single-cell sequencing to link TCR identity, gene expression, antigen specificity, and functional response. Applying this method, we isolate rare reactive T cells, recover their TCRs, and validate five novel MAIT TCRs. All five TCRs, when re-expressed in primary T cells, confer antigen-specific cytokine secretion and cytotoxicity. The top two TCRs were evaluated using an in vivo solid tumor model, demonstrating specific tumor homing and efficacy. This function-first strategy offers a powerful tool to uncover functional TCRs from unconventional T cells, yielding a 100% hit rate when secretion-based validation is included as part of the initial screen, unlocking new opportunities for cell-based immunotherapy.

  PublisherOA PDFDOI

• In vivo CAR engineering for immunotherapy

  Nature reviews. Immunology · 2025-05-16 · 74 citations

  reviewSenior author
  PublisherDOI

• 54Allogeneic HSPC-engineered CD70-directed CAR-NKT cells for renal cell carcinoma targeting tumor, microenvironment, and alloreactive T cells

  The Oncologist · 2025-10-01 · 2 citations

  articleOpen access

  Abstract Background Renal cell carcinoma (RCC), originating from renal epithelium, is the most prevalent type of kidney cancer, accounting for over 90% of all cases. Although targeted therapies such as vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have improved clinical outcomes, approximately 33% of patients still progress to metastatic disease, with a 5-year survival of only 12%. These limitations highlight the urgent need for more effective and Innovative treatment options. Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy targeting CD70 is emerging as an attractive approach for RCC. Clinical trials investigating CD70-directed CAR-T (CAR70-T) cell therapies in RCC are currently underway. Despite their therapeutic potential, current CAR70-T cell therapies face several key limitations. Clinical responses have been modest, likely due to the inherent challenges posed by solid tumors, including antigen heterogeneity and a highly immunosuppressive tumor microenvironment (TME). To overcome these limitations, the development of potent, off-the-shelf CAR70-based cell therapies that can address RCC tumor immune evasion and TME-associated suppression is critically needed. Methods To address these challenges, we employed our previously established hematopoietic stem and progenitor cell (HSPC) gene engineering technology and a clinically guided culture method to generate allogeneic CD70-directed CAR-engineered invariant natural killer T (AlloCAR70-NKT) cells for the treatment of RCC. Through the use of a comprehensive array of experimental models, including primary RCC patient samples, patient-derived tumor cell lines, in vitro functional assays, and both orthotopic and metastatic in vivo xenograft models, we comprehensively evaluated the AlloCAR70-NKT cells, including their manufacturing, in vitro and in vivo antitumor efficacy, mechanism of action, pharmacodynamics and pharmacokinetics, safety, and immunogenicity. Results In this study, we characterize primary RCC patient samples and identify a distinct opportunity to leverage CAR-NKT cells for therapeutic intervention. Utilizing a clinically guided culture method, we successfully generated AlloCAR70-NKT cells from hematopoietic stem and progenitor cells, with high purity, robust expansion, and no fratricide risk. These cells demonstrated multimodal targeting capabilities, including potent cytotoxicity against orthotopic and metastatic RCCs via both CAR- and NK receptor-mediated mechanisms, as well as selective engagement of the immunosuppressive TME through TCR recognition. Notably, host alloreactive T cells express elevated levels of CD70 and can be efficiently targeted by AlloCAR70-NKT cells, leading to enhanced in vivo persistence of therapeutic cells. Conclusions Taken together, our findings support the therapeutic potential of AlloCAR70-NKT cells as a next-generation, off-the-shelf immunotherapy with dual tumor- and TME-targeting functionality, and the added advantage of alloreactive T cell elimination, offering a compelling strategy for treating RCC.

  PublisherOA PDFDOI

• David Baltimore (1938–2025)

  Nature Biotechnology · 2025-12-08

  article1st authorCorresponding
  PublisherDOI

• Screening of selective serotonin reuptake inhibitors from Cyperus rotundus using immobilized neurotransmitter transporter affinity chromatography for antidepressant discovery

  Analytical and Bioanalytical Chemistry · 2025-10-08

  article
  PublisherDOI

• Manufacturing synthetic viscoelastic antigen-presenting cells for immunotherapy

  Nature Protocols · 2025-10-09 · 2 citations

  article
  PublisherDOI

Recent grants

• NIH Grant DP2CA196335

  NIH · $2.3M · 2019

Frequent coauthors

• David Baltimore

  66 shared

• Antoni Ribas

  Parker Institute for Cancer Immunotherapy

  66 shared

• Yan-Ruide Li

  University of California, Los Angeles

  61 shared

• Owen N. Witte

  59 shared

• Donald B. Kohn

  University of California, Los Angeles

  50 shared

• Paula Kaplan‐Lefko

  37 shared

• Jerome A. Zack

  35 shared

• James S. Economou

  University of California, Los Angeles

  35 shared