Cellular Nibbling: How Trogocytosis Shapes Immunity, Cancer, and Infection

Deep inside the immune system, cells are constantly taking bites out of one another. This phenomenon, known as trogocytosis, occurs when two cells come into direct contact and one literally nibbles away patches of the other’s plasma membrane, along with the surface molecules embedded in it. The term derives from the Greek word trogo, meaning to gnaw or nibble, and it describes a process that is fundamentally distinct from the wholesale engulfment of phagocytosis. Rather than consuming an entire cell, the trogocytosing cell acquires fragments of membrane carrying proteins such as major histocompatibility complexes, costimulatory receptors, and intact antigens. A new review published in Molecular Biology Reports by Helal F. Hetta of the University of Tabuk and colleagues synthesizes the rapidly expanding literature on this process, examining how it governs cellular communication, immune regulation, and disease, and asking a provocative question: is trogocytosis a friend or a foe to the immune system?

The answer, according to the accumulating evidence, is that it is emphatically both. On the beneficial side, trogocytosis supports antigen presentation, immune activation, and even the remodeling of neural circuits in the brain. On the harmful side, it contributes to tumor immune evasion, resistance to antibody and cell-based therapies, and the dissemination of intracellular pathogens between host cells. This duality is precisely what makes the process so compelling to immunologists. The same membrane-transfer machinery that allows a dendritic cell to equip a basophil with antigen-presenting capacity can also allow a cancer cell to strip inhibitory receptors from an attacking T cell, or a parasite to devour chunks of its host. Understanding which molecular switches tip trogocytosis from constructive to destructive is now a central goal of the field.

Mechanistically, trogocytosis occupies an intriguing middle ground among the ways cells interact with their neighbors. Unlike phagocytosis, in which a cell internalizes a whole particle or corpse, or endocytosis, which retrieves individual receptors, trogocytosis involves the extraction of membrane patches at a cell-cell junction, often at an immunological synapse. It is also distinct from cell-cell fusion, which merges the cytoplasm of two cells, and from the release and uptake of extracellular vesicles, which transfer material without direct contact. Recent biophysical work has added an important layer of control: a 2025 study in Nature Cell Biology showed that the cortical tension of the target cell regulates how much membrane a macrophage can pull away, while research published in PNAS in 2026 demonstrated that hyperactivation of the small GTPase Rac can convert normally sublethal nibbling into lethal trogocytosis in living animals. These findings suggest that the mechanical and signaling states of both cells jointly determine the outcome of every encounter.

The historical roots of the field stretch back further than many researchers realize. Evidence of antigenic material moving between macrophages and lymphocytes appeared in the early 1970s, and by 1999 a landmark study in Science showed that T cells could acquire and internalize peptide-MHC complexes from the cells they contacted through their T cell receptors. The term trogocytosis itself was formalized in a 2003 Nature Immunology commentary. Since then, the process has been documented across an astonishing range of cell types: T cells, B cells, natural killer cells, antigen-presenting cells, basophils, mast cells, neutrophils, macrophages, microglia, and even amoebae. The breadth of this distribution implies that membrane nibbling is not an evolutionary accident but a deeply conserved strategy for intercellular information transfer.

One of the most consequential roles of trogocytosis lies in antigen presentation through a mechanism called cross-dressing. Cells can acquire preformed peptide-MHC complexes from other cells and display them on their own surfaces without ever processing the antigen themselves. Dendritic cells that cross-dress with viral complexes can drive memory CD8 T cell activation after infection, a phenomenon demonstrated in Nature in 2011. Basophils acquire peptide-MHC class II complexes from dendritic cells and gain the ability to present antigen, while natural killer cells dressed with MHC class II molecules acquired from dendritic cells can regulate CD4 T cell responses. Even mast cells in inflamed skin and group 2 innate lymphoid cells engaged in type 2 immunity have been shown to participate in these MHC-mediated dialogues. Cross-dressing effectively allows the immune system to redistribute antigen-presenting capacity to wherever it is most useful, amplifying or redirecting responses with remarkable economy.

In the nervous system, trogocytosis performs an entirely different kind of housekeeping. Microglia, the resident immune cells of the brain, remodel synapses by nibbling presynaptic terminals through a complement-dependent process, as demonstrated in work published in eLife in 2021. This activity-dependent pruning is essential for the refinement of neural circuits during development and presumably for their maintenance in adulthood. Astrocytes have been observed to phagocytose focal dystrophies from myelin segments, and neurons can even degrade mitochondria from axons through transcellular transfer. These observations blur the classical boundary between phagocytosis and trogocytosis in the central nervous system, suggesting a continuum of nibbling behaviors that sculpt neural architecture without destroying the cells they modify.

The dark side of trogocytosis is perhaps most vivid in cancer. Tumors exploit the process to disarm their attackers. Colon cancer cells have been shown to acquire immune regulatory molecules from tumor-infiltrating lymphocytes, and myeloma cells can strip CD86 or HLA-G from T cells, a transfer associated with poor prognosis. Low-avidity T cells can inhibit the killing activity of high-avidity T cells by trogocytosing their antigen in an antigen-specific manner. The problem extends to the most celebrated cancer therapy of the past decade: chimeric antigen receptor T cells. Landmark work in Nature in 2019 showed that CAR T cells trogocytose the CAR molecule itself, transferring it to tumor cells and thereby stripping the therapeutic cells of their targeting ability while simultaneously arming tumor cells with decoy receptors. Subsequent studies confirmed that trogocytosis of CAR molecules drives T cell dysfunction and tumor antigen escape, and very recent preclinical work suggests that inhibiting cathepsin B can prevent this transfer and augment CAR T cell function, pointing toward a pharmacological fix.

Antibody-based therapies face their own trogocytosis problem. When monoclonal antibodies such as rituximab coat the surface of B cell malignancies, Fc receptor-bearing effector cells can shave the antibody-target complexes off the tumor cell in a reaction aptly named shaving. This removes both the antibody and its target antigen, CD20, from the tumor surface, blunting the therapy’s effectiveness. Neutrophils, it turns out, preferentially perform trogocytosis rather than full phagocytosis of antibody-opsonized chronic lymphocytic leukemia cells, and human tumor-associated macrophages and neutrophils regulate antitumor antibody efficacy through both lethal and sublethal trogocytosis, as reported in Cancer Research in 2024. Yet the same nibbling can be weaponized: macrophage-mediated trogocytosis of antibody-opsonized tumor cells can kill them, neutrophils destroy antibody-coated cancer cells through a process termed trogoptosis, and engineered chimeric antigen receptors that trigger phagocytosis are being designed to direct macrophages against tumors. The dose and timing of antibody administration, and even the afucosylation state of the antibody’s Fc region, influence whether effector cells kill or merely graze their targets.

Infectious agents have also learned to exploit and to suffer trogocytosis. The parasite Entamoeba histolytica uses trogocytosis to bite pieces off host cells, a behavior that contributes directly to cell killing and tissue invasion, as shown in Nature in 2014. Neutrophils, in turn, kill the sexually transmitted parasite Trichomonas vaginalis using trogocytosis, demonstrating that the mechanism cuts both ways across the parasite kingdom. Intracellular bacterial pathogens such as Francisella tularensis can spread from cell to cell via trogocytosis-associated transfer, and the fungus Cryptococcus neoformans moves between macrophages through a related mechanism termed dragotcytosis. Even influenza exploits the process: monocyte-B cell trogocytosis during H5N1 infection increases expression of the alpha-2,3 sialic acid receptor on B cells, enhancing their susceptibility to the virus. NK cells can acquire viral receptors through immunological synapses, sometimes with unpredictable consequences for antiviral immunity.

The therapeutic horizon emerging from this literature is broad. Trogocytosis-based flow cytometry protocols already allow researchers to detect, quantify, and purify antigen-specific live lymphocytes based on the membrane fragments they capture from antigen-presenting cells, and capture of tumor cell membranes facilitates the isolation of tumor-specific cytotoxic T lymphocytes. In transplantation, bidirectional MHC transfer between donor and recipient cells shapes alloreactive responses, and trogocytosis has been implicated in chimerism, prenatal tolerance, and rejection mechanisms regulated by the transcription factor NFATc3. Regulatory T cells can acquire donor-specific tolerance through MHC class II acquisition from plasmacytoid dendritic cells. The CTLA-4 pathway, a cornerstone of checkpoint biology, functions partly through trans-endocytosis of the costimulatory molecules CD80 and CD86, a trogocytosis-like mechanism with direct implications for immunotherapy. As Hetta and colleagues conclude, deciphering the precise molecular rules that govern when cells nibble, what they take, and what the consequences are could pave the way for innovative therapies targeting infections, cancers, and autoimmune disorders. The immune system’s most intimate conversation, it seems, is conducted one bite at a time.

Subject of Research: Trogocytosis as a mechanism of intercellular membrane transfer in immunity, cancer, and infectious disease

Article Title: Trogocytosis: Emerging insights into cellular communication, immunity, and pathogenesis

Article References: Hetta, H. F., El-Maghrabey, M., AlRamadneh, T. N., Bukhari, S. Q., Algammal, A. M., Al-Kadmy, I. M., & Ramadan, Y. N. (2026). Trogocytosis: Emerging insights into cellular communication, immunity, and pathogenesis. Molecular Biology Reports, 53(1), Article 1713. https://doi.org/10.1007/s11033-026-12897-2

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12897-2

Keywords: trogocytosis, immune regulation, antigen presentation, cross-dressing, CAR T cells, tumor immune evasion, monoclonal antibodies, neutrophils, macrophages, microglia, Entamoeba histolytica, immunological synapse