Mechanistically, it is not the disappearance of the macrophages itself that does the trick. The targeting of macrophages stimulates intratumoral type I interferon signaling, which improves the tumor response to cisplatin. The researchers successfully validated the increased type I interferon signaling upon macrophage inhibition in biopsies derived from cancer patients.
Further elimination of immunosuppressive neutrophils in the preclinical breast cancer model enhanced the efficacy of chemotherapy even more, by unleashing an anti-tumor immune response.
These findings highlight the complex regulatory roles of macrophages and neutrophils during chemotherapy response and may contribute to the design of optimal combination therapies with macrophage-targeting drugs.
The immune system and cancer
Ideally, our immune system fights cancer - CD8+ T cells are a case in point - but frequently immune cells help cancer survive and metastasize. For instance, recent studies revealed that tumor-associated macrophages and neutrophils, which are often the most abundant immune cells in tumors, limit the efficacy of chemotherapy.
Bottleneck for a rational combination therapy
Recently, compounds have been developed that target tumor-associated macrophages. However, the mechanisms underlying therapeutic benefit are still poorly understood and it is unknown which chemotherapeutic drugs can be best combined with these macrophage-targeting compounds. This presents a bottleneck for treating patients with a rationally designed combination therapy.
Look for the mechanisms!
In an online publication in Nature Cell Biology, Camilla Salvagno from Karin de Visser's group and other researchers now show how important it is to dive into the cellular and intercellular mechanisms within the complex tumor environment.
