Display options
Cite
Vulpis E, Loconte L, Peri A, et al. Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance. J Extracell Vesicles. 2022;11(1):e12176doi: 10.1002/jev2.12176.
Vulpis, E., Loconte, L., Peri, A., Molfetta, R., Caracciolo, G., Masuelli, L., Tomaipitinca, L., Peruzzi, G., Petillo, S., Petrucci, M. T., Fazio, F., Simonelli, L., Fionda, C., Soriani, A., Cerboni, C., Cippitelli, M., Paolini, R., Bernardini, G., Palmieri, G., Santoni, A., & Zingoni, A. (2022). Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance. Journal of extracellular vesicles, 11(1), e12176. https://doi.org/10.1002/jev2.12176
Vulpis, Elisabetta, et al. "Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance." Journal of extracellular vesicles vol. 11,1 (2022): e12176. doi: https://doi.org/10.1002/jev2.12176
Vulpis E, Loconte L, Peri A, Molfetta R, Caracciolo G, Masuelli L, Tomaipitinca L, Peruzzi G, Petillo S, Petrucci MT, Fazio F, Simonelli L, Fionda C, Soriani A, Cerboni C, Cippitelli M, Paolini R, Bernardini G, Palmieri G, Santoni A, Zingoni A. Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance. J Extracell Vesicles. 2022 Jan;11(1):e12176. doi: 10.1002/jev2.12176. PMID: 34973063.
Copy Download .nbib Format: NLM
Share it on

J Extracell Vesicles. 2022 Jan;11(1):e12176. doi: 10.1002/jev2.12176.

Impact on NK cell functions of acute versus chronic exposure to extracellular vesicle-associated MICA: Dual role in cancer immunosurveillance.

Journal of extracellular vesicles

Elisabetta Vulpis, Luisa Loconte, Agnese Peri, Rosa Molfetta, Giulio Caracciolo, Laura Masuelli, Luana Tomaipitinca, Giovanna Peruzzi, Sara Petillo, Maria Teresa Petrucci, Francesca Fazio, Lucilla Simonelli, Cinzia Fionda, Alessandra Soriani, Cristina Cerboni, Marco Cippitelli, Rossella Paolini, Giovanni Bernardini, Gabriella Palmieri, Angela Santoni, Alessandra Zingoni

Affiliations

  1. Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza' University of Rome, Rome, Italy.
  2. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
  4. Center for Life Nano & Neuro Science, Istituto Italiano di Tecnologia, Rome, Italy.
  5. Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
  6. Neuromed I.R.C.C.S.-Istituto Neurologico Mediterraneo, Pozzilli, Italy.

PMID: 34973063 DOI: 10.1002/jev2.12176

Abstract

Natural killer (NK) cells are innate cytotoxic lymphocytes that play a key role in cancer immunosurveillance thanks to their ability to recognize and kill cancer cells. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed or infected cells. The release of NKG2D ligands (NKG2DLs) in the extracellular milieu through protease-mediated cleavage or by extracellular vesicle (EV) secretion allows cancer cells to evade NKG2D-mediated immunosurveillance. In this work, we investigated the immunomodulatory properties of the NKG2D ligand MICA*008 associated to distinct populations of EVs (i.e., small extracellular vesicles [sEVs] and medium size extracellular vesicles [mEVs]). By using as model a human MICA*008-transfected multiple myeloma (MM) cell line, we found that this ligand is present on both vesicle populations. Interestingly, our findings reveal that NKG2D is specifically involved in the uptake of vesicles expressing its cognate ligand. We provide evidence that MICA*008-expressing sEVs and mEVs are able on one hand to activate NK cells but, following prolonged stimulation induce a sustained NKG2D downmodulation leading to impaired NKG2D-mediated functions. Moreover, our findings show that MICA*008 can be transferred by vesicles to NK cells causing fratricide. Focusing on MM as a clinically and biologically relevant model of tumour-NK cell interactions, we found enrichment of EVs expressing MICA in the bone marrow of a cohort of patients. All together our results suggest that the accumulation of NKG2D ligands associated to vesicles in the tumour microenvironment could favour the suppression of NK cell activity either by NKG2D down-modulation or by fratricide of NK cell dressed with EV-derived NKG2D ligands.

© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

Keywords: MICA; NKG2D; Natural Killer cells; cancer; extracellular vesicles; immune evasion

References

  1. Abruzzese, M. P., Bilotta, M. T., Fionda, C., Zingoni, A., Soriani, A., Vulpis, E., Borrelli, C., Zitti, B., Petrucci, M. T., Ricciardi, M. R., Molfetta, R., Paolini, R., Santoni, A., & Cippitelli, M. (2016). Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells: Role of cMYC-IRF4-miR-125b interplay. Journal of Hematology & Oncology 9, 134. - PubMed
  2. Al-Nedawi, K., Meehan, B., Micallef, J., Lhotak, V., May, L., Guha, A., & Rak, J. (2008). Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nature Cell Biology 10, 619-624. - PubMed
  3. Antonangeli, F., Soriani, A., Ricci, B., Ponzetta, A., Benigni, G., Morrone, S., Bernardini, G., & Santoni, A. (2016). Natural killer cell recognition of in vivo drug-induced senescent multiple myeloma cells. OncoImmunology 5, 10e1218105. - PubMed
  4. Ashiru, O., Boutet, P., Fernández-Messina, L., Agüera-González, S., Skepper, J. N., Valés-Gómez, M., & Reyburn, H. T. (2010). Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes. Cancer Research 70, 481-489. - PubMed
  5. Ashiru, O., López-Cobo, S., Fernández-Messina, L., Pontes-Quero, S., Pandolfi, R., Reyburn, H. T., & Valés-Gómez, M. (2013). A GPI anchor explains the unique biological features of the common NKG2D-ligand allele MICA*008. Biochemical Journal 454, 295-302. - PubMed
  6. Bandari, S. K., Purushothaman, A., Ramani, V. C., Brinkley, G. J., Chandrashekar, D. S., Varambally, S., Mobley, J. A., Zhang, Y., Brown, E. E., Vlodavsky, I., & Sanderson, R. D. (2018). Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior. Matrix Biology 65, 104-118. - PubMed
  7. Borrelli, C., Ricci, B., Vulpis, E., Fionda, C., Ricciardi, M. R., Petrucci, M. T., Masuelli, L., Peri, A., Cippitelli, M., Zingoni, A., Santoni, A., & Soriani, A. (2018). Drug-induced senescent multiple myeloma cells elicit NK cell proliferation by direct or exosome-mediated IL15 trans -presentation. Cancer Immunology Research 6, 860-869. - PubMed
  8. Caivano, A., Laurenzana, I., de Luca, L., la Rocca, F., Simeon, V., Trino, S., D'Auria, F., Traficante, A., Maietti, M., Izzo, T., D'Arena, G., Mansueto, G., Pietrantuono, G., Laurenti, L., Musto, P., & Del Vecchio, L. (2015). High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. Tumor Biology 36, 9739-9752. - PubMed
  9. Caradec, J., Kharmate, G., Hosseini-Beheshti, E., Adomat, H., Gleave, M., & Guns, E. (2014). Reproducibility and efficiency of serum-derived exosome extraction methods. Clinical Biochemistry 47, 1286-1292. - PubMed
  10. Carbone, E., Neri, P., Mesuraca, M., Fulciniti, M. T., Otsuki, T., Pende, D., Groh, V., Spies, T., Pollio, G., Cosman, D., Catalano, L., Tassone, P., Rotoli, B., & Venuta, S. (2005). HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood 105, 251-258. - PubMed
  11. Chan, W. K., Kang, S., Youssef, Y., Glankler, E. N., Barrett, E. R., Carter, A. M., Ahmed, E. H., Prasad, A., Chen, L., Zhang, J., Benson, D. M. Jr, Caligiuri, M. A., & Yu, J. (2018). A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer Immunology Research 6, 776-787. - PubMed
  12. Chiossone, L., Dumas, P.-Y., Vienne, M., & Vivier, E. (2018). Natural killer cells and other innate lymphoid cells in cancer. Nature Reviews Immunology 18, 671-688. - PubMed
  13. Chitadze, G., Bhat, J., Lettau, M., Janssen, O., & Kabelitz, D. (2013). Generation of soluble NKG2D ligands: Proteolytic cleavage, exosome secretion and functional implications. Scandinavian Journal of Immunology 78, 120-129. - PubMed
  14. Clayton, A., Mitchell, J. P., Court, J., Linnane, S., Mason, M. D., & Tabi, Z. (2008). Human tumor-derived exosomes down-modulate NKG2D expression. The Journal of Immunology 180, 7249-7258. - PubMed
  15. Colombo, M., Raposo, G., & Théry, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review of Cell and Developmental Biology 30, 255-289. - PubMed
  16. Daßler-Plenker, J., Reiners, K. S., van den Boorn, J. G., Hansen, H. P., Putschli, B., Barnert, S., Schuberth-Wagner, C., Schubert, R., Tüting, T., Hallek, M., Schlee, M., Hartmann, G., Pogge von Strandmann, E., & Coch, C. (2016). RIG-I activation induces the release of extracellular vesicles with antitumor activity. OncoImmunology 5, e1219827. - PubMed
  17. El-Sherbiny, Y. M., Meade, J. L., Holmes, T. D., McGonagle, D., Mackie, S. L., Morgan, A. W., Cook, G., Feyler, S., Richards, S. J., Davies, F. E., Morgan, G. J., & Cook, G. P. (2007). The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Research 67, 8444-8449. - PubMed
  18. Fauriat, C., Mallet, F., Olive, D., & Costello, R. T. (2006). Impaired activating receptor expression pattern in natural killer cells from patients with multiple myeloma. Leukemia 20, 732-733. - PubMed
  19. Fernández-Messina, L., Ashiru, O., Boutet, P., Agüera-González, S., Skepper, J. N., Reyburn, H. T., & Valés-Gómez, M. (2010). Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands. Journal of Biological Chemistry 285, 8543-8551. - PubMed
  20. Ferrari de Andrade, L., Tay, R. E., Pan, D., Luoma, A. M., Ito, Y., Badrinath, S., Tsoucas, D., Franz, B., May, K. F., Harvey, C. J., Kobold, S., Pyrdol, J. W., Yoon, C., Yuan, G. C., Hodi, F. S., Dranoff, G., & Wucherpfennig, K. W. (2018). Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 359, 1537-1542. - PubMed
  21. Fionda, C., Abruzzese, M. P., Zingoni, A., Cecere, F., Vulpis, E., Peruzzi, G., Soriani, A., Molfetta, R., Paolini, R., Ricciardi, M. R., Petrucci, M. T., Santoni, A., & Cippitelli, M. (2015). The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma. Oncotarget 6, 23609-23630. - PubMed
  22. Gobbo, J., Marcion, G., Cordonnier, M., Dias, A. M. M., Pernet, N., Hammann, A., Richaud, S., Mjahed, H., Isambert, N., Clausse, V., Rébé, C., Bertaut, A., Goussot, V., Lirussi, F., Ghiringhelli, F., de Thonel, A., Fumoleau, P., Seigneuric, R., & Garrido, C. (2016). Restoring anticancer immune response by targeting tumor-derived exosomes with a HSP70 peptide aptamer. Journal of the National Cancer Institute 108, 1-11. - PubMed
  23. Hedlund, M., Stenqvist, A.-C., Nagaeva, O., Kjellberg, L., Wulff, M., Baranov, V., & Mincheva-Nilsson, L. (2009). Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: Evidence for immunosuppressive function. The Journal of Immunology 183, 340-351. - PubMed
  24. Hedlund, M., Nagaeva, O., Kargl, D., Baranov, V., & Mincheva-Nilsson, L. (2011). Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLoS ONE 6, e16899. - PubMed
  25. Jinushi, M., Vanneman, M., Munshi, N. C., Tai, Y.-T., Prabhala, R. H., Ritz, J., Neuberg, D., Anderson, K. C., Carrasco, D. R. & (2007). MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma 105, 1285-1290. - PubMed
  26. Kalluri, R. (2016). The biology and function of exosomes in cancer. Journal of Clinical Investigation 126, 1208-1215. - PubMed
  27. Labani-Motlagh, A., Israelsson, P., Ottander, U., Lundin, E., Nagaev, I., Nagaeva, O., Dehilin, E., Baranov, V., & Mincheva-Nilsson, L. (2015). Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumor Biology 37, 5455-5466. - PubMed
  28. Lanier, L. L. (2015). NKG2D receptor and its ligands in host defense. Cancer Immunology Research 3, 575-582. - PubMed
  29. López-Cobo, S., Campos-Silva, C., Moyano, A., Oliveira-Rodríguez, M., Paschen, A., Yáñez-Mó, M., Blanco-López, M. C., & Valés-Gómez, M. (2018). Immunoassays for scarce tumour-antigens in exosomes: Detection of the human NKG2D-Ligand, MICA, in tetraspanin-containing nanovesicles from melanoma. Journal of Nanobiotechnology 16, 47. - PubMed
  30. Lundholm, M., Schröder, M., Nagaeva, O., Baranov, V., Widmark, A., Mincheva-Nilsson, L., & Wikström, P. (2014). Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: Mechanism of immune evasion. PLoS ONE 9, e108925. - PubMed
  31. Mack, M., Kleinschmidt, A., Brühl, H., Klier, C., Nelson, P. J., Cihak, J., Plachý, J., Stangassinger, M., Erfle, V., & Schlöndorff, D. (2000). Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection. Nature Medicine 6, 769-775. - PubMed
  32. Madera, S., Rapp, M., Firth, M. A., Beilke, J. N., Lanier, L. L., & Sun, J. C. (2016). Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. Journal of Experimental Medicine 213, 225-233. - PubMed
  33. Mathieu, M., Martin-Jaular, L., Lavieu, G., & Théry, C. (2019). Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nature Cell Biology 21, 9-17. - PubMed
  34. McCann, F. E., Eissmann, P., Önfelt, B., Leung, R., & Davis, D. M. (2007). The activating NKG2D ligand MHC Class I-related chain A transfers from target cells to NK cells in a manner that allows functional consequences. The Journal of Immunology 178, 3418-3426. - PubMed
  35. Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., & Kalluri, R. (2015). Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523, 177-182. - PubMed
  36. Molfetta, R., Quatrini, L., Capuano, C., Gasparrini, F., Zitti, B., Zingoni, A., Galandrini, R., Santoni, A., & Paolini, R. (2014). c-Cbl regulates MICA-but not ULBP2-induced NKG2D down-modulation in human NK cells. European Journal of Immunology 44, 2761-2770. - PubMed
  37. Molfetta, R., Quatrini, L., Zitti, B., Capuano, C., Galandrini, R., Santoni, A., & Paolini, R. (2016). Regulation of NKG2D expression and signaling by endocytosis. Trends in Immunology 37, 790-802. - PubMed
  38. Morvan, M. G., & Lanier, L. L. (2016). NK cells and cancer: You can teach innate cells new tricks. Nature Reviews Cancer 16, 7-19. - PubMed
  39. Nakamura, K., Nakayama, M., Kawano, M., Amagai, R., Ishii, T., Harigae, H., & Ogasawara, K. (2013). Fratricide of natural killer cells dressed with tumor-derived NKG2D ligand. Proceedings of the National Academy of Sciences of the United States of America 110, 9421-9426. - PubMed
  40. van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology 19, 213-228. - PubMed
  41. di Noto, G., Bugatti, A., Zendrini, A., Mazzoldi, E. L., Montanelli, A., Caimi, L., Rusnati, M., Ricotta, D., & Bergese, P. (2016). Merging colloidal nanoplasmonics and surface plasmon resonance spectroscopy for enhanced profiling of multiple myeloma-derived exosomes. Biosensors and Bioelectronics 77, 518-524. - PubMed
  42. Ogasawara, K., Hamerman, J. A., Hsin, H., Chikuma, S., Bour-Jordan, H., Chen, T., Pertel, T., Carnaud, C., Bluestone, J. A., & Lanier, L. L. (2003). Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity 18, 41-51. - PubMed
  43. Ogasawara, K., Hamerman, J. A., Ehrlich, L. R., Bour-Jordan, H., Santamaria, P., Bluestone, J. A., & Lanier, L. L. (2004). NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity 20, 757-767. - PubMed
  44. Pazina, T., Macfarlane, A. W., Bernabei, L., Dulaimi, E., Kotcher, R., Yam, C., Bezman, N. A., Robbins, M. D., Ross, E. A., Campbell, K. S., & Cohen, A. D. (2021). Alterations of NK cell phenotype in the disease course of multiple myeloma. Cancers 13(2), 226. - PubMed
  45. Quatrini, L., Molfetta, R., Zitti, B., Peruzzi, G., Fionda, C., Capuano, C., Galandrini, R., Cippitelli, M., Santoni, A., & Paolini, R. (2015). Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells. Science Signaling 8, ra108. - PubMed
  46. Raulet, D. H., Gasser, S., Gowen, B. G., Deng, W., & Jung, H. (2013). Regulation of ligands for the NKG2D activating receptor. Annual Review of Immunology 31, 413-441. - PubMed
  47. Rebmann, V., Schütt, P., Brandhorst, D., Opalka, B., Moritz, T., Reza Nowrousian, M., & Grosse-Wilde, H. (2007). Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients. Clinical Immunology 123, 114-120. - PubMed
  48. Roda-Navarro, P., & Reyburn, H. T. (2007). Intercellular protein transfer at the NK cell immune synapse: Mechanisms and physiological significance. The FASEB Journal 21, 1636-1646. - PubMed
  49. Salih, H. R., Antropius, H., Gieseke, F., Lutz, S. Z., Kanz, L., Rammensee, H.-G., & Steinle, A. (2003). Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102, 1389-1396. - PubMed
  50. Saudemont, A., Burke, S., & Colucci, F. (2010). A simple method to measure NK cell cytotoxicity in vivo. Methods in Molecular Biology 612, 325-334. - PubMed
  51. Segovis, C. M., Schoon, R. A., Dick, C. J., Nacusi, L. P., Leibson, P. J., & Billadeau, D. D. (2009). PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion. The Journal of Immunology 182, 6933-6942. - PubMed
  52. Soriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., di Gialleonardo, V., Cippitelli, M., Fionda, C., Petrucci, M. T., Guarini, A., Foà, R., & Santoni, A. (2009). ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. Blood 113, 3503-3511. - PubMed
  53. Soriani, A., Vulpis, E., Cuollo, L., Santoni, A., & Zingoni, A. (2020). Cancer extracellular vesicles as novel regulators of NK cell response. Cytokine and Growth Factor Reviews 51, 19-26. - PubMed
  54. Sutherland, C. L., Chalupny, N. J., Schooley, K., VandenBos, T., Kubin, M., & Cosman, D. (2002). UL16-Binding Proteins, novel MHC Class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. The Journal of Immunology 168, 671-679. - PubMed
  55. Viaud, S., Terme, M., Flament, C., Taieb, J., André, F., Novault, S., Escudier, B., Robert, C., Caillat-Zucman, S., Tursz, T., Zitvogel, L., & Chaput, N. (2009). Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: A role for NKG2D ligands and IL-15Rα. PLoS ONE 4, e4942. - PubMed
  56. Vulpis, E., Cecere, F., Molfetta, R., Soriani, A., Fionda, C., Peruzzi, G., Caracciolo, G., Palchetti, S., Masuelli, L., Simonelli, L., D'Oro, U., Abruzzese, M. P., Petrucci, M. T., Ricciardi, M. R., Paolini, R., Cippitelli, M., Santoni, A., & Zingoni, A. (2017). Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis. OncoImmunology 6, e1279372. - PubMed
  57. Vulpis, E., Stabile, H., Soriani, A., Fionda, C., Petrucci, M. T., Mariggio’, E., Ricciardi, M. R., Cippitelli, M., Gismondi, A., Santoni, A., & Zingoni, A. (2018). Key role of the CD56lowCD16low natural killer cell subset in the recognition and killing of multiple myeloma cells. Cancers 10(12), 473. - PubMed
  58. Vulpis, E., Soriani, A., Cerboni, C., Santoni, A., & Zingoni, A. (2019). Cancer exosomes as conveyors of stress-induced molecules: new players in the modulation of NK cell response. International Journal of Molecular Sciences 20(3), 611. - PubMed
  59. Wang, Y., Li, H., Xu, W., Pan, M., Qiao, C., Cai, J., Xu, J., Wang, M., & Zhang, J. (2020). BCMA-targeting bispecific antibody that simultaneously stimulates NKG2D-enhanced efficacy against multiple myeloma. Journal of Immunotherapy 43, 175-188. - PubMed
  60. Weissgerber, T. L., Milic, N. M., Winham, S. J., & Garovic, V. D. (2015). Beyond bar and line graphs: Time for a new data presentation paradigm. PLOS Biology 13,e1002128. - PubMed
  61. Wiemann, K., Mittrücker, H.-W., Feger, U., Welte, S. A., Yokoyama, W. M., Spies, T., Rammensee, H.-G., & Steinle, A. (2005). Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo. The Journal of Immunology 175, 720-729. - PubMed
  62. Witwer, K. W., & Théry, C. (2019). Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. Journal of Extracellular Vesicles 8, 1648167. - PubMed
  63. Wu, J. D., Higgins, L. M., Steinle, A., Cosman, D., Haugk, K., & Plymate, S. R. (2004). Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. Journal of Clinical Investigation 114, 560-568. - PubMed
  64. Yang, Y., Chen, Y., Zhang, F., Zhao, Q., & Zhong, H. (2015). Increased anti-tumour activity by exosomes derived from doxorubicin-treated tumour cells via heat stress. International Journal of Hyperthermia 31, 498-506. - PubMed
  65. Zingoni, A., Palmieri, G., Morrone, S., Carretero, M., Lopez-Botel, M., Piccoli, M., Frati, L., & Santoni, A. (2000). CD69-triggered ERK activation and functions are negatively regulated by CD94 /NKG2-A inhibitory receptor. European Journal of Immunology 30, 644-651. - PubMed
  66. Zingoni, A., Cecere, F., Vulpis, E., Fionda, C., Molfetta, R., Soriani, A., Petrucci, M. T., Ricciardi, M. R., Fuerst, D., Amendola, M. G., Mytilineos, J., Cerboni, C., Paolini, R., Cippitelli, M., & Santoni, A. (2015). Genotoxic stress induces senescence-associated ADAM10-dependent release of NKG2D MIC ligands in multiple myeloma cells. The Journal of Immunology 195, 736-748. - PubMed
  67. Zingoni, A., Vulpis, E., Nardone, I., Soriani, A., Fionda, C., Cippitelli, M., & Santoni, A. (2016). Targeting NKG2D and NKp30 ligands shedding to improve NK cell-based immunotherapy. Critical Reviews in Immunology 36, 445-460. - PubMed
  68. Zingoni, A., Molfetta, R., Fionda, C., Soriani, A., Paolini, R., Cippitelli, M., Cerboni, C., & Santoni, A. (2018). NKG2D and its ligands: “One for all, all for one.” Frontiers in Immunology 9, 476. - PubMed
  69. Zingoni, A., Vulpis, E., Cecere, F., Amendola, M. G., Fuerst, D., Saribekyan, T., Achour, A., Sandalova, T., Nardone, I., Peri, A., Soriani, A., Fionda, C., Mariggiò, E., Petrucci, M. T., Ricciardi, M. R., Mytilineos, J., Cippitelli, M., Cerboni, C., & Santoni, A. (2018).MICA-129 dimorphism and soluble MICA are associated with the progression of multiple myeloma. Frontiers in Immunology 9, 926. - PubMed
  70. Zitti, B., Molfetta, R., Fionda, C., Quatrini, L., Stabile, H., Lecce, M., de Turris, V., Ricciardi, M. R., Petrucci, M. T., Cippitelli, M., Gismondi, A., Santoni, A., & Paolini, R. (2017). Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells. Scientific Reports 7(1), 10445. - PubMed
  71. Zocchi, M. R., Tosetti, F., Benelli, R., & Poggi, A. (2020). Cancer nanomedicine special issue review anticancer drug delivery with nanoparticles: Extracellular vesicles or synthetic nanobeads as therapeutic tools for conventional treatment or immunotherapy. Cancers 12(7), 1886. - PubMed

Publication Types