T cells can protect against tumor development, but can become progressively dysfunctional or “exhausted” as cancers progress, thus posing a major barrier to the effectiveness of immunotherapy. Recently, Dr. Lugli and his team discovered rare subpopulations of T cells in healthy individuals as well as in cancer patients that can prevent dysfunction and maintain the potential to eliminate tumors in the long term. These cells are generally referred to as “stem-like” T cells. Unfortunately, immune-suppressing regulatory T cells may also resist dysfunction, thus continuously allowing them to switch off anti-tumor immune responses.
Having already identified stem-like T cells with precision, Lugli now seeks to utilize samples from cancer patients in combination with genomic technologies to study them in detail and reveal unprecedented aspects of their biology. Specifically, he proposes to fine-tune the molecular programs of T cells within tumors, in order to enhance the functionality of anti-tumor T cells while promoting dysfunction in the regulatory T cells on the other side. Then, he will test if these strategies can improve the effectiveness of cell therapies in preclinical models, which could pave the way for their use in humans.
Projects and Grants
T cell stemness and exhaustion in immunosuppression and adoptive cell transfer immunotherapy
Fondazione Humanitas per la Ricerca | All Cancers | 2021
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