Elliott research examines multiple immune pathways for targeting cancer cells
Posted on May 14, 2026 by Lindsay Hughes
Michael R. Elliott, Ph.D., an associate professor of microbiology and immunology at the Frederick P. Whiddon College of Medicine and a researcher at the USA Health Mitchell Cancer Institute, recently published research in the scientific journal Frontiers in Immunology examining how macrophages eliminate antibody-coated cancer cells.
Macrophages are immune cells responsible for engulfing and destroying harmful or damaged cells. The findings provide new insight into how therapeutic antibodies may be designed to improve cancer treatment.
“The main takeaway is that therapeutic antibodies can provoke macrophages to kill cancer cells through more than one route,” Elliott said.
For years, researchers have primarily focused on one immune pathway, known as the Fcγ receptor pathway, to explain how macrophages recognize and destroy antibody-coated cells. Elliott’s research found that the complement system, another part of the immune system traditionally associated with direct destruction of cells, can also drive macrophages to engulf and eliminate cancer cells.
“Our data demonstrate the complement pathway is as effective, if not more effective, in clearing antibody-targeted cells,” Elliott said.
The study also found the two pathways work additively, meaning they can function together rather than redundantly. According to Elliott, engaging both pathways simultaneously may enhance the overall ability of macrophages to destroy cancer cells.
“The idea of balancing Fcγ receptor activity and complement activation could affect how antibodies are engineered and used in the clinic to achieve the most robust and durable target cell clearance,” he said.
Another key finding involved what researchers describe as macrophage “exhaustion.” Elliott explained that macrophages have a limited capacity to continue engulfing antibody-coated cells over time.
Using video microscopy, researchers observed macrophages consuming target cells until their activity slowed or stopped. While complement-mediated engulfment could bypass exhaustion associated with the Fcγ pathway, the complement pathway also eventually reached its own limit.
“That matters because antibody therapies often require macrophages to clear a very large burden of target cells, such as in cancer,” Elliott said.
The findings could eventually influence how future antibody therapies are developed and evaluated. Rather than focusing only on how well an antibody binds to a target, researchers may also consider how effectively it activates multiple immune pathways without overwhelming immune cells responsible for clearance.
“Ultimately, this work points toward antibody therapies that are designed not only to bind the target well, but also to recruit the right innate immune mechanisms in a coordinated way and avoid prematurely exhausting the effector cells that carry out clearance,” Elliott said.
Elliott noted that the study was conducted in controlled laboratory macrophage systems, and future research will examine how the findings translate in living organisms and human immune cells.
The study was published in Frontiers in Immunology, a multidisciplinary journal focused on basic, translational and clinical immunology research.
Elliott joined the University of South Alabama in January 2024. He earned his Ph.D. from Wake Forest University School of Medicine and completed a postdoctoral fellowship at the University of Virginia.