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Samir Mitragotri and his team at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have provided a fresh viewpoint on the difficulties posed by macrophages, a type of white blood cell, in the field of cancer immunotherapy.
Using an engineering perspective, the study published in Applied Physics Reviews outlined the challenges associated with using macrophages in clinical trials. Important new information was uncovered as well, which has the potential to alter the cancer treatment landscape.
Macrophages, well-known for their anti-invasion abilities, have been shown to be effective in cell-based cancer therapy. However, clinical trials using macrophages have all resulted in disappointing results.
Researchers investigated the factors that prevent macrophages, an immune cell type, from reaching cancer cells during treatment. Using tiny cameras and machine learning, they identified a type of immune cell that is more effective than currently used treatments at locating and eliminating tumors. This may pave the way for more efficient strategies for employing our immune systems in the fight against cancer.
“Our engineering approach led us to question whether the poor therapeutic outcome of macrophages in cell therapies can in part originate from their inability to get into the tumor in the first place,”Mitragotri explained.
“And indeed, our results show that different phenotypes exhibit different penetration into the tumor. This provides an interesting physics-based hypothesis for the poor clinical outcome of previously reported macrophage therapies and provides a counter- and complimentary hypothesis to the classical biology-based paradigm,”he added.
Their study found that macrophages move better to reach tumors when they can change their shape. Surprisingly, the macrophages that are best at fighting tumors don't change shape well, making it harder for them to get to the tumors. This discovery could help improve how we use these cells to treat cancer. The study was co-authored by Jennifer Guerriero, assistant professor at Harvard Medical School.