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Manzo Teresa

Young Principal Investigator

  • Research area

    Cancer immunotherapy has been one of the major breakthroughs of cancer treatments. However, despite the impressive results, the incidence of cancer is still raising and the majority of patients will receive little benefit. In the fight against cancer, CD8+ T cells are the soldiers of the immune system which destroy tumor cells. However, they become progressively dysfunctional and no longer able to control tumor outgrowth. One reason for this dysfunctionality is T cells do not receive adequate fuel for their cytotoxic functions. Our research group is interested in understanding the link between T cell metabolism and immunity in cancer. Importantly, our lab focuses on understanding how this dysfunction can be reversed to harness T cells against cancer and improve immunotherapeutic treatment of cancer.

     

    People working in the group

    PhD students
    Silvia Tiberti
    Carina Nava

    Techinician
    Erika Mileti

    Undergrad student
    Lavinia Bertolani


  • Projects

    T cell metabolic exhaustion
    Infiltrating cytotoxic T cells become dysfunctional when they get into the tumor microenvironment. This dysfunctionality is named T cell exhaustion. Recently, we have found that exhausted CD8+ T cells have decreased mitochondrial functionality, which dampens their ability to adapt their metabolism to the poor metabolite microenvironment. Our lab is interested in identifying the mechanisms responsible for ‘metabolic exhaustion’ and how this program impacts T cell functions by performing analyses of T cell metabolic function and bioenergetic flux paralleled by epigenetic and transcriptional profiling.

    T cell metabolism reprogramming
    The tumor microenvironment is a hostile environment for an infiltrating CD8+ T cell. Our group has recently demonstrated that one of the mechanisms by which the tumor microenvironment drives CD8+ T cell exhaustion is by depleting nutrients that are fundamental for sustaining their activity. We are exploring new ways to engineer CD8+ T cells to improve their metabolic fitness and empower them to fight in a poor nutrient microenvironment.

  • Publications

    Manzo T*, Sturmheit T*, Basso V, Petrozziello E, Hess Michelini R, Riba M, Freschi M, Elia AR, Grioni M, Curnis F, Protti MP, Schumacher TN, Debets R, Swartz MA, Corti A, Bellone M and Mondino A. T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNFα Expression and Empower Adoptive Cell Therapy for Solid Tumors. 2017. Cancer Res. 77(3):658-671. * equal contribution.

    Buchan SL*, Manzo T*, Flutter B, Rogel A, Edwards N, Zhang L, Sivakumaran S, Ghorashian S, Carpenter B, Bennett CL, Freeman GJ, Sykes M, Croft M, Al-Shamkhani A and Chakraverty R. OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence. 2015. J Immunol. 194(1):125-133.* equal contribution.

    Hess Michelini R*, Manzo T*, Sturmheit T, Basso V, Rocchi M, Freschi M, Listopad J, Blankenstein T, Bellone M and Mondino A. Vaccine-instructed intratumoral IFN- regression of autochthonous mouse prostate cancer in allogeneic T-cell transplantation. 2013. Cancer Res. 73(15):4641-52. * equal contribution.

PARTNERSHIP

Università degli Studi di Milano Ecancer Medical Science IFOM-IEO Campus

CREDITS

Ministero della Salute Joint Commission International Breastcertification bollinirosa

© 2013 Istituto Europeo di Oncologia - via Ripamonti 435 Milano - P.I. 08691440153 - Codice intermediario fatturazione elettronica: A4707H7

IRCCS - ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO