Tissue infiltrating T lymphocytes in health and disease: new approaches to dissect identity, geography and function of tissutal T cells and to discover new targets for precision immunotherapy

The major focus of my research is the dissection of the heterogeneity of the T cell population infiltrating solid tumors, and how this differs and evolves between primary tumors and metastases. Our knowledge of the human immune system is essentially based on the analysis of lymphocytes isolated from peripheral blood. However, the vast majority (>99%) of effector T lymphocytes reside in peripheral tissues where they contribute to homeostasis or mediate immunopathology in autoimmunity or cancer through poorly defined inflammatory and anti-inflammatory programs. The identification of molecular targets to modulate tissutal T cells is a promising area of investigation with the potential to lead to transformative therapies. In cancer and autoimmunity, tissue T cell subsets exert opposite roles but are pathogenetic in both cases, we can thus describe “loss of function” or “gain of function” of the various T cells subsets in vivo. We are combining single-cell “omics” and in situ analyses to provide an unbiased molecular and geographical landscape of lymphocytes infiltrating primary or metastatic tumors (lung and colon), or inflamed tissues (Rheumatoid Arthritis and Crohn). We are identifying tissue- and disease-specific T-cell transcripts, which are complemented by multiplexed RNA-FISH to obtain maps of spatial networks of tissue T cells. The newly identified genes are then validated with gene and protein expression analyses on large panels of human tissues, and are silenced in T cells in vitro to assess their relevance in T cell function. The intersection of these datasets, the fine dissection of the regulatory networks and modelling of T cell clonal expansion will be used to investigate T cell identity, function and plasticity. In so doing we can differentiate proteins representing effective pharmacological targets because of their necessary and direct role in maintaining T cell functional states from those that may be only sufficient, thus representing less important targets. This approach will generate transformative knowledge on tissutal immune regulation thus identifying new targets for precision immunotherapy.

Projects

  • Phenotypic, molecular and functional characterization of tumor infiltrating T cell complexity and heterogeneity in primary tumors and metastases
  • Establishment of tumoroid models based on co-culturing of organoids (derived from human tumors) and autologous T lymphocytes to study the interplay between tumor cells and immune cells

Team

Nome / NameRuolo / RoleEmail
Valeria Bevilacqua, PhDPost Docbevilacqua@ingm.org
Mauro Bombaci, PhDStaff Scientistbombaci@ingm.org
Susanna CampagnoliLaboratory Techniciancampagnoli@ingm.org
Tanya FabbrisResearcherfabbris@ingm.org
Andrea FavalliPredoctoral studentfavalli@ingm.org
Eugenia Galeota, PhDPost Doc, Bioinformaticiangaleota@ingm.org
Andrea GobbiniResearchergobbini@ingm.org
Renata Grifantini, PhDGroup Leadergrifantini@ingm.org
Paola Gruarin, PhDStaff Scientistgruarin@ingm.org
Raffaele IannuzziResearcheriannuzzi@ingm.org
Mariangela Lorenzo, PhDPost Doclorenzo@ingm.org
Martina Martinovic, PhDPost Docmartinovic@ingm.org
Samuele Notarbartolo, PhDJunior PInotarbartolo@ingm.org
Elisa Pesce, PhDPost Docpesce@ingm.org
Maria Lucia SarnicolaLaboratory Techniciansarnicola@ingm.org
Elena Zagato, PhDScientific Affair Managerzagato@ingm.org

Publications

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