Impaired intratumoral natural killer cell function in head and neck carcinoma
Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immun...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997806/full |
| _version_ | 1811252146259099648 |
|---|---|
| author | Dalila Mele Greta Pessino Giuseppe Trisolini Alberto Luchena Marco Benazzo Marco Benazzo Patrizia Morbini Patrizia Morbini Stefania Mantovani Barbara Oliviero Mario U. Mondelli Mario U. Mondelli Stefania Varchetta |
| author_facet | Dalila Mele Greta Pessino Giuseppe Trisolini Alberto Luchena Marco Benazzo Marco Benazzo Patrizia Morbini Patrizia Morbini Stefania Mantovani Barbara Oliviero Mario U. Mondelli Mario U. Mondelli Stefania Varchetta |
| author_sort | Dalila Mele |
| collection | DOAJ |
| description | Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field.Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors. |
| first_indexed | 2024-04-12T16:30:31Z |
| format | Article |
| id | doaj.art-d70106eab97546b0ba573cc4777af767 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T16:30:31Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d70106eab97546b0ba573cc4777af7672022-12-22T03:25:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.997806997806Impaired intratumoral natural killer cell function in head and neck carcinomaDalila Mele0Greta Pessino1Giuseppe Trisolini2Alberto Luchena3Marco Benazzo4Marco Benazzo5Patrizia Morbini6Patrizia Morbini7Stefania Mantovani8Barbara Oliviero9Mario U. Mondelli10Mario U. Mondelli11Stefania Varchetta12Division of Clinical Immunology and Infectious Diseases, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyUnit of Immunology and General Pathology, Department of Molecular Medicine, University of Pavia, Pavia, ItalyDivision of Otorhinolaryngology, Department of Surgery, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDivision of Otorhinolaryngology, Department of Surgery, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDivision of Otorhinolaryngology, Department of Surgery, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDepartment of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, ItalyPathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, ItalyDepartment of Pathology, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDivision of Clinical Immunology and Infectious Diseases, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDivision of Clinical Immunology and Infectious Diseases, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDivision of Clinical Immunology and Infectious Diseases, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, ItalyDivision of Clinical Immunology and Infectious Diseases, Fondazione Istituto di Ricovero e Cura Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, ItalyNatural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field.Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors.https://www.frontiersin.org/articles/10.3389/fimmu.2022.997806/fulltumor microenvironmentHNSCCnatural killer cellsGITRPD-1NKG2C |
| spellingShingle | Dalila Mele Greta Pessino Giuseppe Trisolini Alberto Luchena Marco Benazzo Marco Benazzo Patrizia Morbini Patrizia Morbini Stefania Mantovani Barbara Oliviero Mario U. Mondelli Mario U. Mondelli Stefania Varchetta Impaired intratumoral natural killer cell function in head and neck carcinoma Frontiers in Immunology tumor microenvironment HNSCC natural killer cells GITR PD-1 NKG2C |
| title | Impaired intratumoral natural killer cell function in head and neck carcinoma |
| title_full | Impaired intratumoral natural killer cell function in head and neck carcinoma |
| title_fullStr | Impaired intratumoral natural killer cell function in head and neck carcinoma |
| title_full_unstemmed | Impaired intratumoral natural killer cell function in head and neck carcinoma |
| title_short | Impaired intratumoral natural killer cell function in head and neck carcinoma |
| title_sort | impaired intratumoral natural killer cell function in head and neck carcinoma |
| topic | tumor microenvironment HNSCC natural killer cells GITR PD-1 NKG2C |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997806/full |
| work_keys_str_mv | AT dalilamele impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT gretapessino impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT giuseppetrisolini impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT albertoluchena impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT marcobenazzo impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT marcobenazzo impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT patriziamorbini impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT patriziamorbini impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT stefaniamantovani impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT barbaraoliviero impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT marioumondelli impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT marioumondelli impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma AT stefaniavarchetta impairedintratumoralnaturalkillercellfunctioninheadandneckcarcinoma |