The age of the macrophage?

Published: 2 June 2021

A new preclinical study highlights the potential of macrophage-based immunotherapy.

“Scientists recognize that tumor-specific T-cells are the best weapon we have against cancer, but immunosuppression prevents them from doing their job. Our treatment uses macrophages like a general to call up an army of T-cell soldiers to kill cancer,” explains Yuan Liu, professor of immunology at Georgia State University, USA, and corresponding author of the new study, in a press release. 

The approach developed by Lui and his colleagues uses macrophages to activate T-cells, and could be applicable against a broad range of cancer types. “Scientists recognize that tumor-specific T-cells are the best weapon we have against cancer, but immunosuppression prevents them from doing their job,” Liu said. “Our treatment uses macrophages like a general to call up an army of T-cell soldiers to kill cancer.”

The research team targeted signal-regulatory protein α (SIRPα), a regulatory membrane glycoprotein that prevents macrophages from eating healthy cells. Cancer cells can hijack this function by expressing a marker to disguise themselves. In a mouse model, SIRPα-deficient macrophages were able to mount a robust immune response, and the treatment was effective when given alongside radiotherapy, without killing large numbers of healthy cells. In the study, the authors identify SIRPα as a “master controller” of immunity in the tumor microenvironment.

“The reason we achieved such a high degree of efficacy is that we directly used the macrophage to mobilize other cells within the body,” said co-author Joby Kidder. “The mounting of a consummate anti-tumor immune response in concert with removing immunosuppressive factors (cells and cytokines) from the tumor microenvironment drastically affected the immune response. By removing SIRPα and combining it with radiotherapy, we elicited such a robust response it essentially cured the cancer.”

The team behind the research believe their approach has the potential to treat a broad range of cancers, and it has already been tested against the NCI-60 cancer panel of 60 human tumor cell lines, with promising results. The researchers now intend to file an IND in hopes of beginning human trials next year.