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Understanding the disappointing performance of macrophage cancer therapy

OCT 06, 2023
Shape switching may hold the key to more effective cancer treatments.
Understanding the disappointing performance of macrophage cancer therapy internal name

Understanding the disappointing performance of macrophage cancer therapy lead image

Macrophages, produced naturally by the body’s immune system, possess an intrinsic ability to infiltrate cancerous tumors. Though numerous cancer treatments designed to leverage this characteristic are in various stages of development, these macrophage therapies have yielded less-than-favorable results.

Adebowale et al. studied the transport of macrophages to tumors to understand the reasons behind this limited clinical success.

Macrophages exist in multiple phenotypes, including the naïve M0 and the activated M1 phenotype. The M1 phenotype, obtained through the addition of cytokines, is used in macrophage injections. The team hypothesized that the trafficking capabilities of macrophages are negatively impacted when the M0 macrophages are converted to M1s.

“Transport is an important consideration,” said author Samir Mitragotri. “Unless the macrophages efficiently traffic into the tumor, they will not be able to exert their anti-tumor effect.”

Cell migration, permeability, and kinetics of tumor entry were quantitatively defined using a 3D assay of a tumor spheroid. Live imaging data and AI algorithms revealed that a significant shape difference existed within a seemingly homogeneous cell population and impacted macrophage migration.

The M0 macrophages exhibited a five times greater ability to cross deep within the tumor spheroids than the M1 macrophages. The M0s also experienced an increased migration through the crowded cellular environment.

“We hope that the rigorous, quantitative approach that we have developed will advance the frontiers of cell therapies and help usher in an era of quantitative, predictive cell therapy,” said Mitragotri.

Source: “Dynamics of macrophage tumor infiltration,” by Kolade Adebowale, Jennifer L. Guerriero, and Samir Mitragotri, Applied Physics Reviews (2023). The article can be accessed at https://doi.org/10.1063/5.0160924 .

This paper is part of the Materials and Technologies for Bioimaging and Biosensing Collection, learn more here .

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