Macrophages are immune cells that work to protect the host from infection or other insults, such as cancer development. However, in cancer, tumor cells engage in a cross-talk with neighbouring macrophages (named tumor associated macrophages, TAM), thereby inducing them to establish an immunosuppressed microenvironment, to promote angiogenesis, tumor growth and metastasis, and to modulate chemotherapy. Therefore, blocking or modifying TAM activity constitutes a potential novel cancer immunotherapy approach.
- To further develop a new cancer therapy to boost the patient’s immune response by targeting macrophages, along with a companion biomarker to select the patients who are most suitable to receive treatment.
Problem to Solve
Obtaining alternative strategies to current cancer treatments would significantly impact patient survival and their quality of life. Immunotherapy is aimed at reactivating the immune system to mount a robust antitumor response, thus providing an alternative or complementary approach to tumor resistance.
However, although successful in certain cases, current immunotherapy treatments need improvement. Two key highly demanded aspects are the development of combination therapies and companion diagnostics to assess who could benefit from treatment. Targeting tumor associated macrophages (TAM) with appropriate therapies could fulfil those two needs.
Maris-Rosa Sarrias and team have identified a therapeutic target in TAMs with great potential for many solid tumors. They then developed a new monoclonal antibody directed at this target, which modifies macrophage responses and has shown antitumor effects in a mouse model of cancer. Their clinical observations in liver cancer further suggest that high expression of the target protein correlates with worse clinical outcome, suggesting the potential of this technology as companion diagnostic.