MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma
The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingl...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2022.2035919 |
| _version_ | 1830403324801712128 |
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| author | Barbara Oliviero Stefania Varchetta Dalila Mele Greta Pessino Roberta Maiello Monica Falleni Delfina Tosi Matteo Donadon Cristiana Soldani Barbara Franceschini Guido Torzilli Gaetano Piccolo Matteo Barabino Enrico Opocher Marcello Maestri Stefano Bernuzzi Kai W. Wucherpfennig Mario U. Mondelli Stefania Mantovani |
| author_facet | Barbara Oliviero Stefania Varchetta Dalila Mele Greta Pessino Roberta Maiello Monica Falleni Delfina Tosi Matteo Donadon Cristiana Soldani Barbara Franceschini Guido Torzilli Gaetano Piccolo Matteo Barabino Enrico Opocher Marcello Maestri Stefano Bernuzzi Kai W. Wucherpfennig Mario U. Mondelli Stefania Mantovani |
| author_sort | Barbara Oliviero |
| collection | DOAJ |
| description | The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA. |
| first_indexed | 2024-12-20T17:06:30Z |
| format | Article |
| id | doaj.art-5aa25f350bde4679a9569a19f98cfd67 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-20T17:06:30Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-5aa25f350bde4679a9569a19f98cfd672022-12-21T19:32:16ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.20359192035919MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinomaBarbara Oliviero0Stefania Varchetta1Dalila Mele2Greta Pessino3Roberta Maiello4Monica Falleni5Delfina Tosi6Matteo Donadon7Cristiana Soldani8Barbara Franceschini9Guido Torzilli10Gaetano Piccolo11Matteo Barabino12Enrico Opocher13Marcello Maestri14Stefano Bernuzzi15Kai W. Wucherpfennig16Mario U. Mondelli17Stefania Mantovani18Division of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoDivision of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoDivision of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoDivision of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoUniversity of PaviaState University of MilanState University of MilanHumanitas Clinical and Research Center, Humanitas UniversityHumanitas Clinical and Research Center, Humanitas UniversityHumanitas Clinical and Research Center, Humanitas UniversityHumanitas Clinical and Research Center, Humanitas UniversityASST Santi Paolo e Carlo, and State University of MilanASST Santi Paolo e Carlo, and State University of MilanASST Santi Paolo e Carlo, and State University of MilanDivision of General Surgery 1, Department of Surgery, Fondazione Irccs Policlinico San Matteo, Pavia, ItalyImmunohematology and Transfusion Service, Department of Diagnostic Medicine, Fondazione IRCCS Policlinico San MatteoDana-Farber Cancer InstituteDivision of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoDivision of Clinical Immunology - Infectious Diseases, Department of Medicine, Fondazione IRCCS Policlinico San MatteoThe major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA.http://dx.doi.org/10.1080/2162402X.2022.2035919natural killer cellsliver cancerinnate immunityadccimmunotherapy |
| spellingShingle | Barbara Oliviero Stefania Varchetta Dalila Mele Greta Pessino Roberta Maiello Monica Falleni Delfina Tosi Matteo Donadon Cristiana Soldani Barbara Franceschini Guido Torzilli Gaetano Piccolo Matteo Barabino Enrico Opocher Marcello Maestri Stefano Bernuzzi Kai W. Wucherpfennig Mario U. Mondelli Stefania Mantovani MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma OncoImmunology natural killer cells liver cancer innate immunity adcc immunotherapy |
| title | MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| title_full | MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| title_fullStr | MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| title_full_unstemmed | MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| title_short | MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| title_sort | mica b targeted antibody promotes nk cell driven tumor immunity in patients with intrahepatic cholangiocarcinoma |
| topic | natural killer cells liver cancer innate immunity adcc immunotherapy |
| url | http://dx.doi.org/10.1080/2162402X.2022.2035919 |
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