SUMMARY
Xinyi Tu, Ph.D., researches cancer biology, therapeutic interventions and the immunologic aspects of oncology. She investigates the intricate mechanisms underlying cancer progression. Dr. Tu identifies new therapeutic targets and develops innovative treatments aimed at improving patient outcomes.
She investigates tumor-induced immunosuppression with the goal of creating innovative strategies that overcome the challenges of immunotherapy resistance.
Dr. Tu uses molecular biology techniques, viral vectors, preclinical models and transgenic mice to explore targets and uncharted mechanisms in developing innovative cancer therapies.
Focus areas
Intracellular programmed death-ligand 1 (PD-L1) in cancer. PD-L1 is a key protein that mediates immunosuppression within the tumor microenvironment and serves as a crucial target for current immunotherapeutic strategies. While PD-L1-targeted immunotherapy has received approval for various cancer types, this treatment only targets the protein's extracellular domains, resulting in an average response rate of approximately 20%.
To augment the efficacy of immunotherapy, it is imperative to delve into the lesser-known functions of PD-L1. Dr. Tu investigates the significant, yet not well explored, role of intracellular PD-L1 to bridge the knowledge gap in PD-L1 biology related to cancer. The new discoveries made by Dr. Tu enrich the current comprehension of immunotherapies and can potentially elevate the response rates to these treatments.
- Fibrosis and extracellular matrix (ECM) stiffness. Cancerous tissue often exhibits an increased accumulation of ECM, leading to tissue stiffening and fibrosis. This heightened stiffness of the ECM is known to exacerbate tumor malignancy and contribute to immunosuppression within the tumor environment. Dr. Tu is exploring new mechanisms by which both tumors and immune cells react to ECM stiffness. She also is identifying and developing innovative therapeutic strategies that may counteract the malignancy and therapy resistance caused by ECM stiffness.
Cancer DNA damage response to enhance therapeutic outcomes. A cell's DNA damage response acts as a guardian of genomic stability, constantly monitoring and repairing DNA damage to prevent mutations and maintain cellular integrity. However, when the DNA damage response is compromised, genetic alterations can accumulate, contributing to the initiation and progression of cancer.
While DNA damage can be lethal to cancer cells, alterations in crucial DNA repair genes may heighten the vulnerability of these cells to treatments such as chemotherapy and radiotherapy. Improving DNA damage response may provide a tactical edge in combating cancer. Dr. Tu is investigating previously uncharted aspects of cancer vulnerability related to DNA damage responses and crafting innovative strategies to heighten tumor sensitivity to these conventional therapies.
- Advancing triple-negative breast cancer (TNBC) therapies. TNBC is an especially aggressive cancer subtype lacking key receptors such as estrogen, progesterone and HER2, which leave it resistant to many standard therapies and prone to metastasis and recurrence. The high mutation load in TNBC, coupled with abundant tumor-infiltrating immune cells, suggests that immunotherapy could be a promising treatment avenue. Yet the prevalent immunosuppressive environment within these tumors often limits the effectiveness of such therapies. Dr. Tu's research identifies the barriers that prevent tumor-infiltrating cells from mounting an effective antitumor response in TNBC. An effective antitumor response may improve patient prognosis and minimize treatment side effects.
Significance to patient care
Dr. Tu investigates critical mechanisms and targets that may lead to innovative cancer therapies in clinical settings. Dr. Tu's research may enhance cancer treatment effectiveness while reducing the adverse effects of cancer therapies, thereby potentially increasing patient survival.
By studying the progression of rare breast cancer variants such as TNBC, which disproportionately impacts African American women, Dr. Tu's work strives to make significant contributions to enhancing the health of African American women and increasing patient well-being.
Professional highlights
- Ad hoc reviewer, Therapeutic Immune Regulation study section, National Cancer Institute, 2024.
- Collaborative Cancer Research Program award, Mayo Clinic Comprehensive Cancer Center and Cancer Research Karolinska Institutet, 2024.
- Early Career Faculty Travel Grant, American Association of Immunologists, 2024.
- Research Excellence Award for the Mayo Employee Resource Group research forum, Mayo Clinic, 2018.