01
LOY & tumor–immune co-evolution
Defining how loss of the Y chromosome and related genomic alterations reshape cancer cells, T-cell states, systemic immunity, and patient outcome.
Academic profile
Xingyu Chen, MD, MSc
Cancer Genomics · Tumor Immunology · Urologic Oncology
Research Bioinformatician · Cedars-Sinai Medical Center · Los Angeles, California
I study how genomic alterations—especially loss of the Y chromosome—reshape tumor–immune ecosystems, drive immune escape, and create opportunities for biomarkers and therapy. Bladder and urothelial cancer provide the clinical anchor; single-cell, spatial, and functional genomics provide the path to mechanism.
Research overview
From patient data to causal biology
I integrate clinical cohorts with cancer genomics, single-cell and spatial multi-omics, computational modeling, and functional genomics. The aim is to identify mechanisms of immune escape and therapy resistance, then translate them into biomarkers and therapeutic hypotheses.
A central theme of my work is loss of the Y chromosome (LOY) in cancer. My research has connected LOY to adaptive immune evasion in bladder cancer and, more recently, to coordinated changes across cancer cells and T cells in pan-cancer tumor ecosystems.
This program extends to T-cell exhaustion and differentiation, AI-enabled radiogenomics, treatment-response biomarkers, and current work in CAR-T systems and perturbational genomics.
Clinical question → Patient cohorts → Multi-omics → Mechanism → Translation
Research areas
Current directions
Three connected areas define my research program, from disease-focused clinical questions to broader mechanisms of tumor immunity.
02
Precision urologic oncology
Developing genomic, immune, and AI radiogenomic approaches for staging, treatment-response prediction, and precision care in bladder and urothelial cancer.
03
T-cell function & CAR-T
Combining patient-derived single-cell states, regulatory modeling, CRISPR perturbation, and functional genomics to identify causal regulators of immune-cell therapy.
Publications
Selected work
Representative publications in tumor immunology, cancer genomics, functional genomics, and precision urologic oncology.
2025
Concurrent loss of the Y chromosome in cancer and T cells impacts outcome
Nature 642, 1041–1050
First author
2023
Y chromosome loss in cancer drives growth by evasion of adaptive immunity
Nature 619, 624–631
Co-first author
2025
Proteotoxic stress response drives T cell exhaustion and immune evasion
Nature 647, 1025–1035
Co-author
2026
ZFP148 is a transcriptional repressor of cytolytic effector CD8⁺ T-cell differentiation
Nature Immunology 27, 827–840
Co-author
2024
MRI/RNA-seq-based radiogenomics and artificial intelligence for more accurate staging of muscle-invasive bladder cancer
International Journal of Molecular Sciences 25, 88
Co-first author
News & recognition
Research in context
Selected coverage and recognition related to my research program.
2025 LOY study featured on Nature’s homepage and covered by Nature News
The accompanying story discussed how Y-chromosome loss in tumors and immune cells may together influence cancer outcome.
2025 · A coordinated tumor–immune event
Nature, Nature News & Views, Nature Genetics and NIH highlighted the finding that concurrent Y-chromosome loss in cancer cells and T cells is associated with immune dysfunction and poor outcome.
Nature News & Views ↗
Nature Genetics ↗
NIH Research Matters ↗
2023 · A mechanism of immune escape in bladder cancer
Nature Reviews Cancer, NIH and the U.S. National Cancer Institute discussed the work as evidence that tumor-cell Y loss promotes T-cell exhaustion while identifying a potential marker of checkpoint-inhibitor response.
Nature Reviews Cancer ↗
NIH Research Matters ↗
NCI Cancer Currents ↗
Background
Medicine, oncology, and computational genomics
Trained in clinical medicine and oncology, I work across clinical, computational, and experimental disciplines. This background supports a research program grounded in patient needs and focused on mechanistic and translational questions.
My academic service includes peer review, editorial activity, and leadership within Prostate Cancer Foundation young-investigator working groups.
2023–Present
Research Bioinformatician ICedars-Sinai Medical Center
2024–2025
Doctoral Research TrainingJohns Hopkins University
2020–2023
Master of Medicine in OncologyXiangya School of Medicine, Central South University
2015–2020
Medical Degree in Clinical MedicineHunan University of Chinese Medicine
Contact
I welcome academic collaborations in urologic oncology, tumor immunology, and computational and translational cancer research.