Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma
Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiologic...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Nature Publishing Group
2024
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| Online Access: | https://hdl.handle.net/10171/68722 |
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| author | Schalper, K.A. (Kurt A.) Rodriguez-Ruiz, M.E. (María Esperanza) Diez-Valle, R. (Ricardo) López-Janeiro, Á. (Álvaro) Porciuncula, A. (Angelo) Idoate, M.A. (Miguel Ángel) Inoges, S. (Susana) Andrea, C.E. (Carlos Eduardo) de Lopez-Diaz-de-Cerio, A. (Ascensión) Tejada-Solis, S. (Sonia) Berraondo, P. (Pedro) Villarroel-Espindola, F. (Franz) Choi, J. (Jungmin) Gurpide, A. (Alfonso) Giraldez, M. (Miriam) Goicoechea, I. (Iosune) Gallego-Perez-Larraya, J. (Jaime) Fernandez-Sanmamed, M. (Miguel) Perez-Gracia, J.L. (Jose Luis) Melero, I. (Ignacio) |
| author_facet | Schalper, K.A. (Kurt A.) Rodriguez-Ruiz, M.E. (María Esperanza) Diez-Valle, R. (Ricardo) López-Janeiro, Á. (Álvaro) Porciuncula, A. (Angelo) Idoate, M.A. (Miguel Ángel) Inoges, S. (Susana) Andrea, C.E. (Carlos Eduardo) de Lopez-Diaz-de-Cerio, A. (Ascensión) Tejada-Solis, S. (Sonia) Berraondo, P. (Pedro) Villarroel-Espindola, F. (Franz) Choi, J. (Jungmin) Gurpide, A. (Alfonso) Giraldez, M. (Miriam) Goicoechea, I. (Iosune) Gallego-Perez-Larraya, J. (Jaime) Fernandez-Sanmamed, M. (Miguel) Perez-Gracia, J.L. (Jose Luis) Melero, I. (Ignacio) |
| author_sort | Schalper, K.A. (Kurt A.) |
| collection | DSpace |
| description | Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-68722 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2024 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-687222024-02-05T06:06:29Z Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma Schalper, K.A. (Kurt A.) Rodriguez-Ruiz, M.E. (María Esperanza) Diez-Valle, R. (Ricardo) López-Janeiro, Á. (Álvaro) Porciuncula, A. (Angelo) Idoate, M.A. (Miguel Ángel) Inoges, S. (Susana) Andrea, C.E. (Carlos Eduardo) de Lopez-Diaz-de-Cerio, A. (Ascensión) Tejada-Solis, S. (Sonia) Berraondo, P. (Pedro) Villarroel-Espindola, F. (Franz) Choi, J. (Jungmin) Gurpide, A. (Alfonso) Giraldez, M. (Miriam) Goicoechea, I. (Iosune) Gallego-Perez-Larraya, J. (Jaime) Fernandez-Sanmamed, M. (Miguel) Perez-Gracia, J.L. (Jose Luis) Melero, I. (Ignacio) Materias Investigacion::Ciencias de la Salud::Oncología Glioblastoma Neoadjuvant nivolumab Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later. 2024-02-02T12:27:14Z 2024-02-02T12:27:14Z 2019 info:eu-repo/semantics/article https://hdl.handle.net/10171/68722 eng info:eu-repo/semantics/closedAccess application/pdf Nature Publishing Group |
| spellingShingle | Materias Investigacion::Ciencias de la Salud::Oncología Glioblastoma Neoadjuvant nivolumab Schalper, K.A. (Kurt A.) Rodriguez-Ruiz, M.E. (María Esperanza) Diez-Valle, R. (Ricardo) López-Janeiro, Á. (Álvaro) Porciuncula, A. (Angelo) Idoate, M.A. (Miguel Ángel) Inoges, S. (Susana) Andrea, C.E. (Carlos Eduardo) de Lopez-Diaz-de-Cerio, A. (Ascensión) Tejada-Solis, S. (Sonia) Berraondo, P. (Pedro) Villarroel-Espindola, F. (Franz) Choi, J. (Jungmin) Gurpide, A. (Alfonso) Giraldez, M. (Miriam) Goicoechea, I. (Iosune) Gallego-Perez-Larraya, J. (Jaime) Fernandez-Sanmamed, M. (Miguel) Perez-Gracia, J.L. (Jose Luis) Melero, I. (Ignacio) Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title | Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title_full | Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title_fullStr | Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title_full_unstemmed | Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title_short | Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| title_sort | neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma |
| topic | Materias Investigacion::Ciencias de la Salud::Oncología Glioblastoma Neoadjuvant nivolumab |
| url | https://hdl.handle.net/10171/68722 |
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