Lund University Cancer Center Distinguished Seminar

2 Apr '19
Time
10:00 - 11:00
Location
Auditorium, Medicon Village
Organiser
Lund University Cancer Center and Medicon Village

“Memory and effector T cell differentiation at single cell resolution: implications for anti-tumor immune responses”

Enrico Lugli, Humanitas Clinical and Research Center, Milan, Italy

Time and location: April 2nd at 10am, MV Lecture Hall (Hörsalen), coffee and cake at 9:30am

Biography:

Enrico Lugli is the Principal Investigator of the Translational Immunology Lab and also Head of the Flow Cytometry Core at Humanitas Clinical and Research Center in Milan, Italy. After receiving his PhD in Immunology studying T cell immune responses and homeostasis during the course of HIV infection, he moved to the National Institute of Health in Bethesda, MD, USA to join the ImmunoTechnology Section directed by Dr. Mario Roederer. There, he studied the molecular mechanisms involved in the maintenance of long-lived T cell immunity in humans and non-human primates. In collaboration with Dr. Thomas Waldmann, he moved Interleukin (IL)-15, a cytokine capable of activating anti-tumor effector cells, from the preclinical level to the first-in-human phase I clinical trial in patients with solid cancers. His current scientific interests are focused on understanding the biological mechanisms at the basis of memory T cell responses and homeostasis in humans and how this information can be exploited to favor immune recovery, anti-tumor and anti-viral responses in patients with cancer.

Abstract:

In response to immune activation, naive CD8+ T cells generate a large number of effector cells capable of migrating to peripheral tissues and killing infected cells. When antigen is cleared, a small population of antigen-specific T cells survives and differentiates into a pool of long-lived memory T cells that is highly diverse at the transcriptional, metabolic, epigenetic and functional levels. Single cell technologies are revolutionizing biology and are opening new insights on how biological processes are regulated. We recently extended flow cytometry capability to measure up to 30-parameters on single cells and are combining it with single cell RNA sequencing to investigate T cell differentiation in physiology and pathology. In this talk, I will show how human effector differentiation is shaped by heterogeneity at the level of the preimmune repertoire and how a diverse progeny of memory T cells is present at the level of the immune microenvironment in human cancer and influences disease progression.

Selected publications:

  1. Pilipow K, Scamardella E, Puccio S, Gautam S, De Paoli F, Mazza EM, et al. Antioxidant metabolism regulates CD8+ T memory stem cell formation and antitumor immunity. JCI Insight 2018; 3.
  2. Brummelman J, Mazza EMC, Alvisi G, Colombo FS, Grilli A, Mikulak J, et al. High-dimensional single cell analysis identifies stem-like cytotoxic CD8(+) T cells infiltrating human tumors. The Journal of experimental medicine 2018; 215:2520-35.
  3. Zanon V, Pilipow K, Scamardella E, De Paoli F, De Simone G, Price DA, et al. Curtailed T-cell activation curbs effector differentiation and generates CD8(+) T cells with a naturally-occurring memory stem cell phenotype. European journal of immunology 2017; 47:1468-76.
  4. Lugli E, Hudspeth K, Roberto A, Mavilio D. Tissue-resident and memory properties of human T-cell and NK-cell subsets. European journal of immunology 2016; 46:1809-17.
  5. Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, et al. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 2015; 125:2855-64.

Contact information

Christina Sakellariou, christina.sakellariou@immun.lth.se

Files

enricolugli_20190402.pdf