Research Group
Allavena Group
Cellular Immunology Lab
Our research group studies tumor-associated macrophages, cells of the innate immunity able to promote tumor progression, and investigates how these cells could be targeted or re-educated, paving the way to innovative therapeutic approaches to cancer.
The challenge
Macrophages are, to a varying extent, crucial components of the tumor microenvironment of virtually all types of cancer, and contribute to tumor progression at different levels: by sustaining genetic instability and nurturing cancer stem cells, by facilitating the metastatic process and by hindering adaptive immunity. Many strategies are currently under investigation to alter tumor-associated macrophage (TAM) recruitment or to rewire them towards antitumor behavior. Such TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy, while, at the same time, TAM-dependent biomarkers could help us discriminate different patient/disease profiles and choose the most effective treatments.
Main research areas
Understanding tumor-associated macrophages
We study tumor-associated macrophages (TAMs): novel macrophage-derived products have been identified and are now investigated for their functional role on tumor cells. Examples include molecules inducing cancer cell motility and metastatic ability, as well as regulators of cancer cell stemness. Another research project concerns the role of macrophages at sites where tumor cells invade peripheral nerves and of the neuro-immune axis in the regulation of tumor growth.
Targeting tumor-associated macrophages
As macrophages are involved in several key steps of cancer progression, we developed strategies to target TAMs in pre-clinical therapeutic settings. These included, in the past, the direct depletion of TAMs with a registered chemotherapeutic agent: trabectedin, demonstrated to be selectively cytotoxic for monocytes-macrophages. More recently we are interested in novel nanotechnology approaches to target TAMs with functionalized, drug-loaded Nanoparticles.
Tumor biology and prognostic biomarkers
A main research line is the identification of immune-associated variables with clinical relevance in human tumors, such as pancreatic and colorectal cancers, liver metastases and mesothelioma. We analyze relevant bio-specimens, including tumor samples, blood and other fluids, to quantify immune cells and their products, including metabolites. The final goal is to identify markers associated with distinct clinical profiles and validate their usefulness for the early diagnosis and precision prognosis of tumors and their response to therapies.
Selected publications
Polymeric nanocapsules loaded with poly(I:C) and resiquimod to reprogram tumor-associated macrophages for the treatment of solid tumors.
An in vitro model for osteoarthritis using long-cultured inflammatory human macrophages repeatedly stimulated with TLR agonists.
hMENA isoforms regulate cancer intrinsic type I IFN signaling and extrinsic mechanisms of resistance to immune checkpoint blockade in NSCLC.
Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages.
Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.
High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis.
Macrophages as tools and targets in cancer therapy.
Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer.
Inhibition of tumor-associated macrophages by trabectedin improves the antitumor adaptive immunity in response to anti-PD-1 therapy.
Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity.
The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33.
Differential role of Interleukin-1 and Interleukin-6 in K-Ras-driven pancreatic carcinoma undergoing mesenchymal transition.
Tumour-associated macrophages as treatment targets in oncology.
Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient.
Role of macrophage targeting in the antitumor activity of trabectedin.
Group members
