Newly published discoveries have revealed possibilities for the treatment of cancer by targeting tumour-associated macrophages (TAMs) in the tumour microenvironment (TME).
The founding scientists behind Edinburgh-based Macomics, Dr Luca Cassetta and Professor Jeff Pollard, detail the seminal discoveries in macrophage biology over the past 50 years in a major Perspectives review in Nature Reviews Cancer.
The TME is now recognised to be inundated with immune cells, of which TAMs are often the most abundant by cell number.
Clinical correlative data and preclinical studies of cancers have now shown that both tumour-associated and metastasis associated macrophages play an important role in promoting cancer.
Improved intravital imaging (IVI) capabilities in preclinical models and newer technologies such as spatial transcriptomics and multicolour multiplex immunofluorescence and mass spectrometry are enabling mapping at single-cell resolution the TME cellular landscape.
Myeloid targeting strategies are now in the clinic and show early signs of efficacy as mono and combination therapies.
“We are entering a golden era of discoveries, resulting in the manipulation of the TME, and in particular TAM biology, that will allow immunotherapy to be widely applicable to many if not all cancers”, conclude Dr Cassetta and Prof Pollard, adding: “Recent technological advances have enabled decoding of TAM complexity in human tumours; such important steps will allow a more precise TAM targeting in the clinic. The next big challenge will be to apply these technologies on clinical samples coming from patients who failed previous cancer therapies to assess TAM evolution during cancer treatment resistance.”
Company will take learnings forward
Macomics is an immuno-oncology company set up to take up take forward these learnings and opportunities.
Prof Pollard is a Principal Investigator at the MRC Centre for Reproductive Health (MRC-CRH), University of Edinburgh. Formerly its director, he has been investigating the roles of macrophages in development, tissue repair and cancer for almost 30 years.
He is co-founder of and remains advisor to Macomics. Dr Cassetta previously worked with Prof Pollard and is now VP immunology at Macomics, having left his role at the University of Edinburgh to join the company full time.
Dr Steve Myatt, Macomics CEO said: “We are passionate about the therapeutic potential of targeting macrophages for the treatment of cancer. Our vision is to develop a new approach to targeting the immunosuppressive tumour microenvironment, that exploits disease-specific macrophage biology to harness the power of the entire immune system.”