Innate Immunity in Inflammation and Cancer Lab

The challenge

Neutrophils are the most abundant circulating white blood cells in humans, accounting for 50–70% of the total leukocytes. However, neutrophils are “unsung heroes” in immunology and they have long been disregarded as short-lived effector cells with activities restricted to the acute inflammatory response and to the elimination of extracellular pathogens. Our group participated in the revision of this dogma, revealing that neutrophils are important players in the activation and regulation of both innate and adaptive immune responses. We defined a neutrophil-UTCαβ axis important for resistance against selected tumors. The role played by neutrophils and UTCαβ in health and diseases, including in cancer, remains poorly understood but a deeper insight into their diversity and role in anti-tumor responses could uncover new potential targets for cancer therapy.

Main research areas

Dynamics, heterogeneity and plasticity of neutrophils in cancer

A deep and accurate analysis of tumor-associated neutrophils (TANs) would allow to determine the molecular mechanisms triggering the neutrophil-dependent anti-tumor response. Using state-of-the-art technology including transcriptomic analysis, imaging mass cytometry and flow cytometry we will determine the dynamics of neutrophil recruitment and polarization in different tumors, including carcinogenesis, genetically engineered mouse models of cancer and models of metastasis. In addition, we will explore the role of neutrophils in immunotherapy and define their underestimated significance, plasticity and role in human cancer.

Heterogeneity, population and clinical significance of double negative T cells in cancer

We recently unveiled (Cell, 2019) a novel axis in antitumor immunity, in which neutrophils regulated the polarization of a poorly understood subset of unconventional T cells. Using a genetic approach complemented by adoptive cell transfer, we found that neutrophils were essential for the activation of an interferon-γ-dependent pathway of anti-tumor immune resistance, associated with polarization of a subset of CD4- CD8- UTCαβ. We operationally called these cells double negative TCRβ⁺ T cells. These cells possess an innate-like phenotype and antitumor potential in vivo. We aim to dissect their biology and immunobiology and to unveil the mechanisms sustaining their activation and anti-tumor activity. We will study their potential role in therapy and their clinical significance.