RESEARCH GROUP

Raffaella Bonecchi

Our research is broadly aimed at understanding the role of chemokines and chemokine receptors in the modulation of leukocyte migration and function in cancer.

We study several chemokine receptors, but we are particularly focused on dissecting the pathological function of one “atypical” chemokine receptors, ACKR2. Our work has revealed that ACKR2 is a key regulator of inflammatory chemokine networks in tumors and regulate the trafficking of innate leukocytes from the bone marrow to the tumor or metastatic sites.

In addition, we are focused on the role of chemokines in the activation and polarization of neutrophils, central players of the innate immune response.

 

Active ongoing projects:

 

  1. Targeting chemokine receptors to harness neutrophil anti-tumor immune response

Immunotherapy is starting to give impressive results in melanoma and glioblastoma patients but a large fraction of patients is still not responding. Neutrophils are an important component of tumor infiltrate and neutrophilia is often found in the blood of cancer patients. For this reason, understanding how to harness neutrophil antitumoral potential will improve treatment outcomes for patients.

With this project we want to identify the role of chemokine receptors in the antitumoral activity of neutrophils in order to improve standard cancer therapies and immunotherapies. Furthermore, we expected to find if chemokine receptors could be used to track neutrophil subpopulations with different effector functions in cancer patients in order to provide an important prognostic factor.

 

  1. Study of the role of ACKR2 in trafficking and activation of anti-metastatic innate immunity

The general aim of the project is to identify the role of ACKR2 in mediating the release from the bone marrow and the maturation of innate immune cells endowed with antimetastatic activity. Since ACKR2 acts as a checkpoint for the release and maturation of neutrophils with antimetastatic activity, we will study if ACKR2 is affecting also release and maturation of other innate immune cells. In addition we will study the possible synergism of ACKR2 inhibition with immunotherapy using preclinical models of metastatic melanoma and lung cancer.

 

  1. Role of the atypical chemokine receptor ACKR2 in colon cancer metastasis

Because of ACKR2 role in regulating the inflammatory trafficking, we decide to deeper investigate its implication in colorectal carcinoma, the third most common cancer worldwide with a tendency to metastasize primarily in liver and lungs. Our aim is testing the hypothesis that ACKR2 negatively affects immune response in metastatic CRC by modulating CCR1-5 chemotaxis of innate immune cells. In order to achieve this purpose, we will use different murine models of liver and lung CRC metastases and we will dissect the phenotype of immune infiltrate into the lesions, characterizing immune cells by multiparametric FACS analysis and RNA sequencing. These preclinical models will be useful to dissect CRC metastatization pathway and to develop novel targets for immunotherapy.

Group Members