RESEARCH GROUP

Enrico Lugli

  • Enrico Lugli Principal Investigator, Laboratory of Translational Immunology - Head, Flow Cytometry Core View More

Contact Information

  • Address
    Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milano
  • Telephone
    +39 02 8224 5143
  • Fax
    +39 02 8224 5101
  • E-mail
    enrico.lugli@humanitasresearch.it

The Laboratory of Translational Immunology (LTI) is 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 favour immune recovery, anti-tumor and anti-viral responses in patients with cancer. The group uses high dimensional approaches including single cell RNA sequencing, 30-parameter flow cytometry and computational approaches to dissect the complexity of the immune system at the level of single cells in physiology and following treatment with innovative drugs.

Regulation of T cell stemness

Memory T cells are thought to be maintained in the long term by simultaneous self-renewal and multipotency, in a way similar to somatic stem cells. We have originally identified T cells with stem-like properties in humans (TSCM) that display enhanced anti-tumor immunity upon adoptive transfer compared to conventional central and effector memory T cells. Our current effort is to identify the molecular basis of stemness, so to promote stem-like properties in anti-tumor T cells, such as chimeric antigen receptor (CAR)-redirected T cells, and thus improve persistence and functionality.

High-dimensional single cell analysis of anti-tumor T cell responses

Checkpoint blockade has definitively proven that the immune system can mediate cancer regression, but only a subset of patients responds to therapies. As several subsets of pro-or anti-tumoral T cells may infiltrate human tumors, we use single cell approaches and computational analysis to dissect such complexity. By combining single cell RNAseq and 30-parameter flow cytometry, we can map anti-tumor immune responses in dozens of cancer patients, and identify those features that are associated with immune control of cancer progression.

We use high-content single cell approaches to dissect the complexity of T cell immune responses in physiology and in the context of cancer and viral infections. Searching through subsets is not just fundamental for basic immunology, as it can lead to a better understanding on the molecular process at the basis of memory T cell differentiation, but is also important to identify the T cell populations that can mediate optimal T cell responses against cancer and viral infections. In this context, we have recently determined that early differentiated naïve and TSCM cells retain substantial reservoir of reduced glutathione, a major cellular anti-oxidant. Treatment of T cells activated in effector-polarizing conditions in the presence of anti-oxidants hindered effector differentiation while preserving stem-like functions, and enhanced anti-tumor immunity of CAR-redirected T cells upon adoptive transfer (Pilipow, JCI Insight, 2018). The lab recently advanced the capability of flow cytometry to measure up to 30 parameters in single cells and solved some of the issues involved in the visualization of such complex data (Mazza, Cytometry A, 2018). Despite still limited in its analysis capability compared to single cell RNAseq, 30-parameter FACS is capable to analyze millions of cells in a relatively short time, thus making it the optimal technique for immunomonitoring of a large number of patients’ samples. In this way, we recently identified a rare subset of CD8+ T cells infiltrating human tumors displaying partial exhaustion but retaining stem-like features and cytotoxic activity (Brummelman, J Exp Med, 2018). We are currently profiling dozens of specimens from different types of cancers to identify immune correlates of protection from disease progression as well as novel targets of immunotherapy.

    Selected Publications

  • Enrico Lugli Publications

    Selected Publications Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, Schietinger A, Schumacher TN, Schwartzberg PL, Sharpe AH, ...

Group Members