Xin Lu John M. and Mary Jo Boler Collegiate Associate Professor

Tumor Microenvironment, Tumor Immunity and Immunotherapy, Metastasis, Multi-Omics
Xin Lu

Research Interests:

Understanding and targeting the tumor microenvironment is at the forefront of current basic and translational cancer research. Targeting tumor microenvironment is closely related to tumor immunology and immunotherapy, one of the most exciting and rapidly evolving areas of cancer research. An intense focus of research in our lab is to investigate the molecular and cellular mechanisms underlying the cancer ─ tumor microenvironment crosstalk, in particular interactions between cancer cells and the myeloid compartment, in both primary tumors and metastases to bone and other organs. We propose that the efficacy of immune checkpoint blockade drugs (e.g. anti-CTLA4, anti-PD1 antibodies) on refractory metastatic cancer can be potently enhanced when combined with other therapy modalities, including targeted therapy that specifically antagonize immunosuppressive activities yet preserve T cell functions in the tumor microenvironment. Recent publications from the Lu lab firmly establish that immunosuppressive neutrophils (also known as polymorphonuclear myeloid-derived suppressor cells, PMN-MDSCs), play the predominant role in inducing the exhaustion of effector T cells in the tumor microenvironment across multiple solid tumors. A number of mechanisms and targeting strategies of PMN-MDSCs have been reported by the Lu lab including the CXCR1/2 inhibitor SX-682, the tyrosine kinase inhibitor cabozantinib, and the cyclooxygenase-2 inhibitor celecoxib, which may open new avenues to sensitize advanced malignancies to immune checkpoint blockade therapy. Dr. Lu also investigates and develops novel immuno-therapeutics and molecularly-targeted therapeutics, including antibody-drug conjugates, chimeric antigen receptor (CAR)-engineered NK cells and small molecules targeting transcription coactivators that promote metastasis. Through creating new models of immunosuppressive neutrophils and animal models with key genes knocked-out in neutrophils, we are on the path to identify more specific and potent therapeutic strategies on the “bad” immune compartment of solid tumors.

We investigate both cancer-cell-intrinsic and -extrinsic mechanisms of immune evasion and immunotherapy resistance. Our research has revealed a number of targetable mechanisms on how the oncogenic signaling in neoplastic cells (“cancer-cell-intrinsic”) exerts the cell non-autonomous functions to control the cancer-immune interactome in solid tumors. For example, our publication is Science Immunology (2023) found that cancer cell expression of the chromatin effector Pygo2 promotes immunotherapy resistance by restraining tumor T cell infiltration and cytotoxicity. Another publication on Cell Metabolism (2023) reveal how tumor-infiltrating neutrophils escape from ferroptosis (a newly identified iron-dependent non-apoptosis cell deathh) through the aconitate decarboxylase 1 (Acod1)-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis. To make these findings, we employ diverse types of models and techniques, such as genetically engineered mice and cell models, functional genomics, experimental therapeutics, and cutting-edge experimental and computational methodologies (single cell RNA-seq, spatial transcriptomics, high-throughput drug and CRISPR/cas9 screen, molecular digital pathology, multi-omics integration, etc.).

We are equally interested in the most prevalent cancer types that both women and men suffer from (breast, prostate, pancreas, kidney), as well as rare cancer types such as penile cancer and Von Hippel-Lindau disease (VHL). As part of the Center for Rare and Neglected Diseases (CRND), our mission is to understand and eliminate cancer in the near future through bench-to-bedside translational research and partnership with drug discovery powerhouses.

Our research is supported by federal grants, private foundations and institutional funds. We are actively recruiting graduate students, postdoctoral fellows and undergraduate students, who are passionate about transforming cancer medicine to benefit human health and society. Please email Dr. Lu directly if you are interested in joining us!



  • John M. and Mary Jo Boler Associate Professor, Department of Biological Sciences, University of Notre Dame, IN 2022-Present
  • John M. and Mary Jo Boler Assistant Professor, Department of Biological Sciences, University of Notre Dame, IN 2017-2022
  • Junior Chair, Boler-Parseghian Center for Rare and Neglected Diseases; Full member, Harper Cancer Research Institute (HCRI); Cluster Chair, Cellular & Molecular Biology Cluster, Integrated Biomedical Sciences (IBMS) PhD Program; Member, Chemistry-Biochemistry-Biology Interface (CBBI) Program; Member, Warren Family Center for Drug Discovery; Member, Eck Institute for Global Health (EIGH); Member, Advanced Diagnostics & Therapeutics (AD&T), University of Notre Dame
  • Full Member, Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren Simon Cancer Center (NCI-designated comprehensive cancer center)
  • Instructor, Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 2014-2016
  • Jane Coffin Childs Postdoctoral Fellow. Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 2011-2014  (Mentor: Ronald A. DePinho)
  • Jane Coffin Childs Postdoctoral Fellow. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 2010-2011 (Mentor: Ronald A. DePinho)
  • Ph.D. (Molecular Biology), Princeton University, Princeton, NJ 2004-2010  (Mentor: Yibin Kang)
  • B.S. (Biological Sciences), Tsinghua University, Beijing, China 2000-2004


Recent Papers:

View all of Xin Lu's Publications with link to PubMed:

Important Note: Below only shows the papers with Xin Lu as the corresponding author and/or first author since 2016. Lu lab also actively co-publishes works with collaborating chemists, bioengineers and bioinformaticians, so please click the link above to see our full list of publications on PubMed.

  • Huang T, Cheng X, Chahoud J, Sarhan A, Tamboli P, Rao P, Guo M, Manyam G, Zhang L, Xiang Y, Han L, Shang X, Deng P, Luo Y, Lu X, Feng S, Ferrer MM, Alan Wang Y, DePinho RA, Pettaway CA, Lu X. Effective combinatorial immunotherapy for penile squamous cell carcinoma. Nat Commun. 2020 May 1;11(1):2124. doi: 10.1038/s41467-020-15980-9. PubMed PMID: 32358507; PubMed Central PMCID: PMC7195486.
  • Lu X, Pan X, Wu CJ, Zhao D, Feng S, Zang Y, Lee R, Khadka S, Amin SB, Jin EJ, Shang X, Deng P, Luo Y, Morgenlander WR, Weinrich J, Lu X, Jiang S, Chang Q, Navone NM, Troncoso P, DePinho RA, Wang YA. An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer. Cancer Res. 2018 Jul 15;78(14):3823-3833. doi: 10.1158/0008-5472.CAN-17-3564. Epub 2018 May 16. PubMed PMID: 29769196; PubMed Central PMCID: PMC6381393.
  • Wang G, Lu X, Dey P, Deng P, Wu CC, Jiang S, Fang Z, Zhao K, Konaparthi R, Hua S, Zhang J, Li-Ning-Tapia EM, Kapoor A, Wu CJ, Patel NB, Guo Z, Ramamoorthy V, Tieu TN, Heffernan T, Zhao D, Shang X, Khadka S, Hou P, Hu B, Jin EJ, Yao W, Pan X, Ding Z, Shi Y, Li L, Chang Q, Troncoso P, Logothetis CJ, McArthur MJ, Chin L, Wang YA, DePinho RA. Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression. Cancer Discov. 2016 Jan;6(1):80-95. doi: 10.1158/2159-8290.CD-15-0224. PubMed PMID: 26701088; PubMed Central PMCID: PMC4707102.