In this Webinar, You Will Learn:
• The role of the tumor microenvironment in cancer immunology and immunotherapy, focusing on cancer-cell-intrinsic
and -extrinsic mechanisms of immune evasion and immunotherapy resistance.
• Strategies to improve the efficacy of immune checkpoint blockade drugs by combining with other therapy modalities.
• The application of single-cell technologies, such as single-cell RNA sequencing, to study changes in immunocytes in
response to experimental therapeutics, offering insights into the genomic, genetic and molecular mechanisms of
tumor immunology.
About this Webinar:
T-cell-oriented cancer immunotherapy, most triumphed by immune checkpoint blockade (ICB) and CAR-T therapies, has transformed the cancer treatment landscape and benefited many patients. However, de novo and acquired resistance to these therapies remains a significant challenge. Our recent works illuminate some immunosuppression mechanisms in prostate cancer and breast cancer, where both cancer-cell-intrinsic and -extrinsic pathways contribute to the formation of an immunosuppressive microenvironment, suggesting a concerted targeting strategy is required to overcome immunosuppression and enable immunotherapy efficacy.
We identified emerging strategies, including molecularly targeted therapy and dietary interventions. The use of single-cell technologies greatly facilitates understanding the immunocyte changes in response to the experimental therapeutics and helps guide the following steps to improve the efficacy further. The goal of our research is ultimately tipping the survival curves to a complete “flat tail” – the dream of cancer immunotherapy.
About Dr. Lu
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 Lu 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. Dr. Lu 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, Lu's team are on the path to identify more specific and potent therapeutic strategies on the “bad” immune compartment of solid tumors.
Learn More about Dr. Lu and His Lab: https://biology.nd.edu/people/xin-lu/
Dr. Lu's Recent Publications:
• Zhao Y, Liu Z, Liu G, Zhang Y, Liu S, Gan D, Chang W, Peng X, Sung ES, Gilbert K, Zhu Y, Wang X, Zeng Z, Baldwin H, Ren G, Weaver J, Huron A, Mayberry T, Wang Q, Wang Y, Diaz-Rubio ME, Su X, Stack MS, Zhang S, Lu X, Sheldon RD, Li J, Zhang C, Wan J, Lu X. Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1. Cell Metabolism. 2023 Oct 3;35(10):1688-1703.e10. doi: 10.1016/j.cmet.2023.09.004. PubMed PMID: 37793345; PubMed Central PMCID: PMC10558089.
• Zhu Y, Zhao Y, Wen J, Liu S, Huang T, Hatial I, Peng X, Al Janabi H, Huang G, Mittlesteadt J, Cheng M, Bhardwaj A, Ashfeld BL, Kao KR, Maeda DY, Dai X, Wiest O, Blagg BSJ, Lu X, Cheng L, Wan J, Lu X. Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer. Sci Immunol. 2023 Mar 17;8(81):eade4656. doi: 10.1126/sciimmunol.ade4656. Epub 2023 Mar 10. PubMed PMID: 36897957.
• Zhu Y, Duong L, Lu X, Lu X. Cancer-cell-intrinsic mechanisms shaping the immunosuppressive landscape of prostate cancer. Asian J Androl. 2023 Mar-Apr;25(2):171-178. doi: 10.4103/aja202283. Review. PubMed PMID: 36367020.
• Lu X, Liu X, Celià-Terrassa T, Ren G. Editorial: Stromal and immune microenvironment in breast cancer metastasis. Front Immunol. 2022;13:1104362. doi: 10.3389/fimmu.2022.1104362. eCollection 2022. PubMed PMID: 36561756; PubMed Central PMCID: PMC9763918.
• Rahmy S, Mishra SJ, Murphy S, Blagg BSJ, Lu X. Hsp90β inhibition upregulates interferon response and enhances immune checkpoint blockade therapy in murine tumors. Front Immunol. 2022;13:1005045. doi: 10.3389/fimmu.2022.1005045. eCollection 2022. PubMed PMID: 36341371; PubMed Central PMCID: PMC9630337.
