Researchers from Uppsala University made a big discovery that could change the future of cancer immunotherapy. They found that CAR-T cells, which are modified immune cells, can give their important CAR molecules to other T cells in the tumour microenvironment. This unusual condition, known as trogocytosis, has the potential to greatly impact the efficacy of CAR-T cell therapy. Their findings, published in Science Immunology, call into question long-held views about how immune cells interact and trade proteins, potentially leading to new therapeutic techniques.

Trogocytosis, a process in which immune cells exchange surface chemicals, has fascinated scientists for years. However, the regulatory mechanisms driving this behaviour have remained unknown—until now.

Car-T cells, a groundbreaking treatment for diseases such as leukaemia and lymphoma, are genetically designed to express CAR molecules on their surfaces, allowing them to target and eradicate cancer cells. According to the latest study, these CAR molecules can travel from designed cells to non-modified T cells in the tumour microenvironment, modifying how immune responses are regulated.

"Our study disproves the old hypothesis that an integral membrane protein can only be exchanged if it binds to a corresponding receptor on another immune cell," explains Stefano Barbera, postdoctoral researcher at the Department of Immunology, Genetics, and Pathology and lead author of the paper. "Instead, we found that it is the membrane region surrounding the molecule that determines whether it can be transferred or not." 

This discovery directly undermines a long-held immunological premise. Previously, the assumption was that trogocytosis required a binding partner on the recipient cell to share a protein. The Uppsala researchers discovered, however, that CAR molecules without such binding partners nonetheless experienced trogocytosis, contradicting popular wisdom.

"The fact that CAR molecules do not require a binding partner on other T cells further disproves the old hypothesis about how trogocytosis is regulated," explains Anna Dimberg, a senior author of the study. "We are very excited to contribute new biological insights into this process." 

Despite the promise of CAR-T therapy, there are still challenges—some patients may not respond, while others have serious side effects. Understanding and regulating trogocytosis could help to fine-tune these treatments for better results.

"The biological role of CAR trogocytosis in CAR-T cell therapy remains unknown," admits Magnus Essand, the study's other senior author. "Now that we know how to regulate it, we can design CAR molecules with or without the ability to trogocytose and test them in advanced models, and hopefully, in clinical trials."

This finding raises important questions: Could increased trogocytosis increase CAR-T cell persistence in the body, making therapy more effective? Or might restricting this mechanism eliminate undesirable side effects? The capacity to manage this transfer process could be the key to optimising CAR-T therapy for various malignancies and patient demands.

Although this study contributes significantly, researchers still need to evaluate the practical implications of their findings. Clinical trials will be necessary to determine whether treating trogocytosis improves patient outcomes. If successful, this study could lead to the next generation of CAR-T therapies that are more effective, safer, and tailored to specific patient responses.

With immunotherapy at the forefront of cancer treatment developments, studies like this highlight the promise of precision medicine. Scientists are paving the way for medicines that not only combat cancer more effectively but also reduce global risks by uncovering the hidden intricacies of immune cell communication.