Tumors evade immune surveillance by triggering immune suppression. Cancer immunotherapy aims at reestablishing the immune surveillance and counteract immune suppression to achieve clinical responses. Our laboratory investigates mechanisms by which innate and adaptive T cells are recruited in the antitumor response and strategies to harness their functions for more efficacious immunotherapies.

We are following two research lines:

1. Redirecting “non-conventional” T cells that recognize lipid antigens presented by CD1 molecules against malignant cells. CD1 molecules are non-polymorphic MHC-I-related molecules expressed by mature myeloid and B cells. CD1-restricted T cells recognize bacterial-derived or stress-related cell-endogenous lipids, and are implicated in the control of infections, cancer and auto-immunity. We showed that CD1d-restricted iNKT cells indirectly control cancer progression by enforcing immunostimulatory programs in myelomonocytic cell populations in the tumour microenvironment (Cortesi Cell Reports 2018). This prompted their engineering with tumor-specific TCRs or CARs to generate bispecific effectors targeting protumor myeloid populations and cancer cells at the same time (Delfanti Sci Immunol 2022) We also showed that a group of CD1c self-reactive T cells recognizes a lipid antigen (mLPA) overrepresented in cancer cells (Lepore J Exp Med. 2014). This supported the design of a donor-unrestricted adoptive cell therapy strategy targeting any CD1c-expressing hematological malignancy with T or iNKT cells engineered with mLPA-specific TCRs (Consonni Nat Commun 2021).

2. Investigating conventional tumor-specific, MHC-restricted T cell responses specific for peptide antigens, and the local immune landscape and its dynamic modification by current therapies. We focus on two different cancer types: .i. Hepatic metastases from colorectal adenocarcinoma CRC); ii. Locally advanced esophageal adenocarcinoma (EAC) upon neoadjuvant chemo-radiation (NAC/R) therapy (Arbore Cancer Res. 2023). Both cancers are investigated by deep profiling methods including spatially resolved omics.