July 21, 2024

Engineering Approach Unveils Promising Macrophage Phenotype for Targeting Tumors

In the realm of cancer treatments, cell therapy has emerged as a promising approach. One type of cell that has garnered attention is macrophages, a type of white blood cell known for their ability to infiltrate tumor cells and eradicate pathogens. However, despite their potential in the lab, macrophages have failed to deliver desired results in clinical trials. To understand this discrepancy, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have taken an engineering perspective to investigate the potential physical barriers preventing macrophages from effectively targeting tumors.

Led by Samir Mitragotri, Professor of Bioengineering and Biologically Inspired Engineering at SEAS, the research team employed a combination of microscopy and machine learning. They discovered that a specific phenotype of macrophage exhibited superior tumor-targeting capabilities compared to others, contrary to the phenotype commonly used in clinical cancer therapies.

There are three simplified phenotypes of macrophages: M0, M1, and M2. Among these, M1 macrophages have traditionally been viewed as the most effective for fighting tumors and have consequently been utilized in cell therapies. However, their performance in clinical trials has been disappointing.

The team at SEAS assessed the ability of each macrophage phenotype to navigate through a complex hydrogel and reach a tumor in a controlled setting. Kolade Adebowale, a postdoctoral fellow at SEAS and the first author of the paper, explained, “We wanted to measure how well the transport mechanics and GPS of these different macrophages worked in a complex environment. We found that the M1 phenotype, which is known for its anti-tumor properties, appeared to have difficulty finding its targets, almost as if its GPS wasn’t working. On the other hand, the M0 phenotype demonstrated superior navigation skills, as if it had an exceptional map.”

The researchers observed a correlation between the shape-changing abilities of macrophages and their transport efficiency. The M0 phenotype, which exhibited high shape-shifting abilities, displayed a greater capability to reach the tumor, while the M1 phenotype, which had inferior shape-shifting abilities, struggled to do so.

Adebowale commented, “Our study demonstrates that the reduced transport of M1 macrophages compared to M0 macrophages is correlated with their reduced ability to undergo shape transformations. We hope that these findings shed new light on the biophysics of macrophage migration and the delivery of macrophage cell therapies.”

Utilizing macrophages to stimulate anti-tumor immune responses in human tumors holds tremendous potential, and ongoing clinical trials are investigating this approach. Jennifer Guerriero, Assistant Professor at Harvard Medical School and lead investigator of Brigham and Women’s Hospital Breast Oncology Program, who co-authored the study, highlighted the significance of the findings. She stated, “Surprisingly, we discovered that macrophages resembling the M0 phenotype were the most efficient at reaching their target. These findings are likely to have an immediate impact on clinical trials and are expected to shape the next generation of macrophage-mediated therapies.”

In conclusion, the engineering approach taken by the researchers at SEAS has revealed that the choice of the macrophage phenotype plays a crucial role in their ability to target tumors effectively. These findings offer new insights into macrophage migration, providing a foundation for the development of improved macrophage-based therapies for cancer treatment.

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1. Source: Coherent Market Insights, Public sources, Desk research
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