Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Mattei, Fabrizio; Andreone, Sara; Spadaro, Francesca; Noto, Fumitoshi; Tinari, Antonella; Falchi, Mario; Piconese, Silvia; Afferni, Claudia; Schiavoni, Giovanna

doi:10.1016/j.isci.2022.105110

Cited by 9 publications

(4 citation statements)

References 80 publications

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“…CR3 has previously been shown to mediate neutrophil trogocytosis of cancer cells, including cells from breast cancer, 55 neuroblastoma, 56 and renal cell carcinoma. 57 Furthermore, reports have shown a role for CR3 in eosinophil trogocytic killing of cancer cells, 58 and in neutrophil trogocytic killing of T-cells. 59 Furthermore, the involvement of CR3 in trogocytosis and killing of Tv, suggests yet another role for CR3 among its other estab-…”

Section: Discussionmentioning

confidence: 99%

Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells

Trujillo,

Flores,

Romero

et al. 2024

Parasite Immunology

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Trichomonas vaginalis (Tv) is a parasite that causes trichomoniasis, a prevalent sexually‐transmitted infection. Neutrophils are found at the site of infection, and can rapidly kill the parasite in vitro, using trogocytosis. However, the specific molecular players in neutrophil killing of Tv are unknown. Here, we show that complement proteins play a role in Tv killing by human neutrophil‐like cells (NLCs). Using CRISPR/Cas9, we generated NLCs deficient in each of three complement receptors (CRs) known to be expressed on human neutrophils: CR1, CR3, and CR4. Using in vitro trogocytosis assays, we found that CR3, but not CR1 or CR4 is required for maximum trogocytosis of the parasite by NLCs, with NLCs lacking CR3 demonstrating ~40% reduction in trogocytosis, on average. We also observed a reduction in NLC killing of Tv in CR3 knockout, but not CR1 or CR4 knockout NLCs. On average, NLCs lacking CR3 had ~50% reduction in killing activity. We also used a parallel approach of pre‐incubating NLCs with blocking antibodies against CR3, which similarly reduced NLC killing of parasites. These data support a model in which Tv is opsonized by the complement protein iC3b, and bound by neutrophil CR3 receptor, to facilitate trogocytic killing of the parasite.

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Section: Discussionmentioning

confidence: 99%

Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells

Trujillo,

Flores,

Romero

et al. 2024

Parasite Immunology

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“…However, this might not be the case for tumor receptors like HER2, because similarly to our present results, it has been observed that NK cells co-cultured with trastuzumab-opsonized HER2+ breast cancer cells can acquire HER2 receptor via trogocytosis and exhibit higher expression of CD107a than non-HER2-trogocytosed NK cells ( 47 ). In addition, NK cells are capable to obtain the tyrosine kinase receptor TYRO3 from leukemia cells in vitro and in vivo , displaying higher levels of activation markers, enhanced cytotoxicity and interferon-γ secretion ( 49 ), thus providing opposing evidence that tumor receptor trogocytosis on NK cells could also translate into gain of anti-tumor activity and effector function ( 56 ). This study was focused on the identification of NK cell subsets harboring trogocytosed markers from breast cancer cells, and even if experiments to elucidate the functional outcome of the acquisition of these markers by trogocytosis are pending to perform, we observed high levels of CD107a and low levels of PD1 expression on these NK cells from BC patients, which considering the mentioned literature is consisting with high anti-tumor function of these NK cells.…”

Section: Discussionmentioning

confidence: 99%

NK cells in peripheral blood carry trogocytosed tumor antigens from solid cancer cells

et al. 2023

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The innate immune lymphocyte lineage natural killer (NK) cell infiltrates tumor environment where it can recognize and eliminate tumor cells. NK cell tumor infiltration is linked to patient prognosis. However, it is unknown if some of these antitumor NK cells leave the tumor environment. In blood-borne cancers, NK cells that have interacted with leukemic cells are recognized by the co-expression of two CD45 isoforms (CD45RARO cells) and/or the plasma membrane presence of tumor antigens (Ag), which NK cells acquire by trogocytosis. We evaluated solid tumor Ag uptake by trogocytosis on NK cells by performing co-cultures in vitro. We analyzed NK population subsets by unsupervised dimensional reduction techniques in blood samples from breast tumor (BC) patients and healthy donors (HD). We confirmed that NK cells perform trogocytosis from solid cancer cells in vitro. The extent of trogocytosis depends on the target cell and the antigen, but not on the amount of Ag expressed by the target cell or the sensitivity to NK cell killing. We identified by FlowSOM (Self-Organizing Maps) several NK cell clusters differentially abundant between BC patients and HD, including anti-tumor NK subsets with phenotype CD45RARO+CD107a+. These analyses showed that bona-fide NK cells that have degranulated were increased in patients and, additionally, these NK cells exhibit trogocytosis of solid tumor Ag on their surface. However, the frequency of NK cells that have trogocytosed is very low and much lower than that found in hematological cancer patients, suggesting that the number of NK cells that exit the tumor environment is scarce. To our knowledge, this is the first report describing the presence of solid tumor markers on circulating NK subsets from breast tumor patients. This NK cell immune profiling could lead to generate novel strategies to complement established therapies for BC patients or to the use of peripheral blood NK cells in the theranostic of solid cancer patients after treatment.

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“…Transcript abundance, as measured by RNAseq, does not perfectly correlate with the production and membrane presence of the associated protein [74][75][76][77] . However, transcriptomics provides a snapshot of the cell's signaling frozen in time, offering invaluable insights.…”

Section: Limitationsmentioning

confidence: 99%

Barking Up the Right Tree: Immune Checkpoint Signatures of Human and Dog Cancers

Kocikowski,

Yébenes Mayordomo,

Alfaro

et al. 2024

Preprint

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In the quest for improved therapeutics targeting immune checkpoints (ICs), we turn to spontaneously developing dog (canine) cancers, which are unique models that genetically and clinically mirror human equivalents. Despite its potential, canine cancer immunology remains largely unexplored. Here, we examine the RNA-seq-based expression of 44 ICs across 14 canine cancer types and an extensive human dataset. We unveil diverse canine IC expression patterns and unique human IC signatures that reflect the histological type and primary site of cancer. We uncover a striking similarity between canine brain cancers, osteosarcoma, and their human counterparts, identifying them as prospective immunotherapy models. Four ICs—CD160, A2AR, NKG2A, and OX40—are key to the differences observed between species. Moreover, individual patient IC signatures exhibit varying alignment with their respective cancer types, a finding with profound implications for personalized human therapy. This exploration illuminates new aspects of canine and human cancer immunology, setting the stage for discoveries at their crossroads.

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Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Cited by 9 publications

References 80 publications

Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells

Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells

NK cells in peripheral blood carry trogocytosed tumor antigens from solid cancer cells

Barking Up the Right Tree: Immune Checkpoint Signatures of Human and Dog Cancers

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