Coupe transversale d’un mélanome avec les MTA CD163 (macrophages associés aux tumeurs) colorés en vert, les vaisseaux sanguins colorés en rouge et le noyau des cellules coloré en gris. © 2019 Etzerodt et al.

An international team led by Toby Lawrence, Inserm researcher at Unit 1104 Center of Immunology Marseille-Luminy (Inserm / CNRS / Aix-Marseille Université), has developed a potential therapy to reduce tumor size, where previous drugs have failed. Its findings have been published in Journal of Experimental Medicine.

Tumors develop from abnormal cells in the body that continue to grow, forming lumps. While these can be benign, they can also become malignant and lead to cancer.

Malignant tumors, infiltrated by immune cells known as macrophages, usually help the body’s immune defenses. But tumor-associated macrophages (TAMs) are manipulated by cancer cells to not only contribute to the growth and spread of tumors in the body, but also to the suppression of our natural immune defenses against them.

It was in order to counteract this dual mechanism in the growth and spread of tumors that an international team including researchers from Inserm and King’s College London have designed a therapy that targets TAMs without suppressing other macrophages. In a study published in Journal of Experimental Medicine, the researchers explain how they were able to target the “bad” TAMs without suppressing the body’s own natural defenses.

Other recent developments in cancer therapy include drugs known as immune checkpoint inhibitors (ICIs) which have revolutionized the field, especially for melanoma patients. However, patients who do respond to ICI therapy experience severe side effects and over 70% of patients do not respond at all.

In this study, the authors used mouse models of melanoma resistant to ICI therapy.

They were able to specifically target the “bad” TAMs, responsible for massive immune cell recruitment, and significantly reduce tumor size.

According to Toby Lawrence, the Inserm researcher who led the study, this research could lead to the creation of a drug to specifically kill TAMs.

“We were astounded to see how effective targeting a specific subset of TAMs was in reducing tumor growth in this model, where ICI therapy had no impact, he states. This study not only provides a new strategy for targeting specific TAM subsets in the clinic, but also shows why it’s important to target specific TAM subsets and not other macrophages that help anti-tumor immune responses.”