Immunology, Transplantation and Infectious diseases

Experimental Immunology

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Head of Unit

Paolo Dellabona

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The Dellabona/Casorati lab investigates T cell responses in tumor immunosurveillance and immunotherapy, by combining a variety of approaches in pre-clinical and clinical models.

Research activity

The research topics of the Unit are:

  1. Deciphering the role in cancer of “non-conventional” T cells that recognize lipid antigens presented by CD1 molecules, non-polymorphic MHC-I-related molecules expressed by mature myeloid and B cells. CD1-restricted T cells are abundant, recognize bacterial-derived or cell-endogenous lipids, and are implicated in the control of infections, cancer and auto-immunity. We have shown that invariant Natural Killer T cells (iNKT), a subset of CD1d- restricted T cells displaying innate effector functions, rewire the prostate cancer microenvironment leading to cancer control. We are unraveling the mechanisms of this modulation in different solid and hematological malignancies and investigating ways to potentiate iNKT cell control of the tumor microenvironment for cancer immunotherapy. We have also identified a group of CD1c-restricted T cells that recognize a leukemia-associated lipid antigen and kill acute leukemia frequently expressing CD1c. We are investigating this T cell response in newly generated CD1c transgenic mice, and developing an “off-the-shelf” adoptive cell therapy strategy with T cells engineered with CD1c-restricted, leukemia-specific TCRs, which can be applied to all patients with CD1c+ leukemia recurrence following bone marrow transplantation.
  2. Investigating conventional MHC-restricted T cell responses specific for tumor- associated peptide antigens, and local immune contextures, in mediating cancer control in patients following neoadjuvant (pre-surgery) therapy. Failure to respond to this therapy is in fact a major unmet clinical need of solid tumors and this study may help stratify patients and inform novel approaches to improve clinical outcomes. We are assessing locally advanced oesophageal cancer, which is a paradigm for this clinical problem.