Massimiliano (Max) Mazzone graduated in Medical Biotechnology at the Medical School of the University of Torino, Italy, and then performed his PhD in Cell Science and Technologies at the Institute for Cancer Research of Torino, under the supervision of Prof. Comoglio. Already during his PhD at the Institute for Cancer Research and Treatment of Torino, Italy, Prof. Mazzone achieved results on the role of Met in cancer progression and tumor angiogenesis. His thesis work resulted in two first author and co-author publications in top journals, namely Cancer Cell (Michieli, Mazzone et al., 2004; Pennacchietti et al., 2003), Journal of Clinical Investigation (Mazzone et al., 2004), PNAS (Arena et al., 2007; Petrelli et al., 2006) and one review article in FASEB Journal (Mazzone et al., 2006). He joined the lab of Prof. Peter Carmeliet as a Postdoc in November 2006 (supported by an EMBO Long Term fellowship, and simultaneously selected by FEBS as well, ultimately opting for the former one).
During his postdoctoral studies, Prof. Mazzone accumulated a vast amount of knowledge on angiogenesis, hypoxia and metastasis, and he developed extraordinary abilities to become an excellent independent investigator. Focusing on vascular biology, he identified and characterized a new endothelial cell phenotype during the perfusion of hypoxic tissues (Mazzone et al., Cell, 2009; Leite de Oliveira et al., Cancer Cell, 2012, Ehling et al, Circulation Research, 2019). These findings were very influential and opened up a new concept that tumor oxygenation and vessel normalization shield cancer cells out of the blood stream and improve delivery of chemotherapeutic drugs to the tumor. He additionally demonstrated that excessive vessel pruning after anti-angiogenic treatment can instead worsen tumor hypoxia and drug delivery.

Since he started his independent research at VIB, he focused on the response of inflammatory cells to hypoxia, metabolites and cytokine surges, aiming to restore blood flow in conditions as cancer and ischemia (Rolny et al., Cancer Cell, 2011; Casazza et al., Cancer Cell, 2013; Wenes et al., Cell Metabolism, 2016; Takeda et al., Nature, 2011; Hamm et al., EMBO Mol Med, 2013). He pioneered the concept that localization of tumor-associated macrophages (TAMs) is determinant   for their pro-vascular function, immune phenotype and for the anti-tumor T cell response (Wenes et al., Cell Metabolism, 2016; Bieniasz-Krzywiec et al., Cell Metabolism, 2019; Casazza et al., Cancer Cell, 2013; Casazza & Mazzone, Oncoimmunology, 2014; Palmieri et al., Cell Rep, 2016), and has shown that some of these inflammatory fingerprints can be exploited for disease detection and follow-up in cancer  patients  or  can  be  used  to  predict  disease response to targeted therapies (Hamm et al., Gut, 2016; Finisguerra et al., Nature, 2015). As a result of his research, qualitative rewiring of innate immunity has replaced the original concept of quantitative inflammatory cell disruption. With his new concept that hypoxic TAMs are the pro-tumoral TAMs that have to be turned off while feeding the anti-tumor properties of TAMs in normoxia, he moved away from the more dogmatic definitions of M1 and M2 polarized macrophages. Indeed, his work shows that hypoxia fine-tunes the immune phenotype of macrophages without affecting the expression of canonical polarization markers.  As well, a subset of TAMs characterized by surface markers and a specific metabolism cuffs the lymphatic vessels in the tumors promoting new sprouts and favouring lymphoinvasion and lymphatic metastasis (Bieniasz-Krzywiec et al., Cell Metabolism, 2019). Mazzone’s work has also contributed to the study of macrophages a the metastatic niche (Celus et al., Cell Reports, 2015).

With his research, Prof. Mazzone is increasing the knowledge on the molecular and cellular mechanisms controlling inflammatory cell skewing and the significance of this process in cancer. Although metabolic competition between stromal cells and cancer cells are by now described, he was the first to show an important role of metabolic competition between two different stromal compartments, namely macrophages and endothelial cells, during the stabilization of the newly formed vascular branch (Wenes et al., Cell Metabolism, 2016). Similarly, cancer cells under glucose or oxygen deprivation overcome cell death by remodeling their metabolic and oxygen-sensing machinery (Di Conza et al., Cell Rep, 2017a; Di Conza et al., Cell Rep, 20017b).

Finally, the Laboratory of Prof. Mazzone has efficiently transferred the knowledge in cancer to other diseases such as inflammation, infections and tissue degeneration where immune cell responses are important to reestablish homeostasis (Takeda et al., Nature, 2011; Hamm et al., EMBO Mol Med, 2013; Finisguerra et al., Nature, 2015; Shang et al., Nature, 2020; Virga et al., Science Advances, 2021).

Prof. Mazzone is a competitive young investigator with a truly outstanding scientific record (162 articles in peer-reviewed journals, with over 14000 citations, and an H-index of 55), building an internationally highly visible career. He is in the editorial board of several journals (e.g., Cancer Research, Immunometabolism, etc.), and an active member in several evaluating commissions (e.g., the Belgian Foundation against Cancer, Cancer Research UK, etc.) and reviewers for numerous granting agencies and peer-reviewed journals. He received prestigious grants (ERC Starting Grant, and ERC Consolidator Grant, ERC PoC, etc.) and international prizes (EMBO Young Investigator, AstraZeneca, Chiara D’Onofrio, etc.). In 2021, he was nominated an EMBO Member. A tangible contribution of his forward-thinking is indicated by the attempt of translating his findings into the clinic. He  licensed a blood monocyte-based test for Colorectal Cancer detection (Colonokit™) to the Belgian company DNA Lytics. He has co-developed a drug with a dual function as MET inhibitor and immunostimulator that went into a Phase II clinical trial in 2018, and he has more than 5 ongoing drug discovery programs in collaboration with VIB Drug Discovery Sciences and CD3 (Leuven). His cooperation with pharmaceutical industry include CoBioRes, Thrombogenics, Jansen Pharmaceutica, Merus and many more. He is one of the scientific founders of the oncology company Oncurious and Montis Biosciences and obtained seed capital as a solo founder for a third spin-off. Looking at what he achieved so far, it is very clear that he has created a new way of thinking about molecular and cellular partners controlling inflammatory cell skewing and their significance in cancer and response to chemo-/immunotherapy.

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