Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches
The interpretation of the presence and function of immune infiltration in glioblastoma (GBM) is still debated. Over the years, GBM has been considered a cold tumor that is less infiltrated by effector cells and characterized by a high proportion of immunosuppressive innate immune cells, including GB...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6156 |
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| author | Elena Anghileri Monica Patanè Natalia Di Ianni Irene Sambruni Martina Maffezzini Micaela Milani Luisa Maddaloni Bianca Pollo Marica Eoli Serena Pellegatta |
| author_facet | Elena Anghileri Monica Patanè Natalia Di Ianni Irene Sambruni Martina Maffezzini Micaela Milani Luisa Maddaloni Bianca Pollo Marica Eoli Serena Pellegatta |
| author_sort | Elena Anghileri |
| collection | DOAJ |
| description | The interpretation of the presence and function of immune infiltration in glioblastoma (GBM) is still debated. Over the years, GBM has been considered a cold tumor that is less infiltrated by effector cells and characterized by a high proportion of immunosuppressive innate immune cells, including GBM-associated microglia/macrophages (GAMs). In this context, the failure of checkpoint inhibitors, particularly in recurrent GBM (rGBM), caused us to look beyond the clinical results and consider the point of view of immune cells. The tumor microenvironment in rGBM can be particularly hostile, even when exposed to standard immunomodulatory therapies, and tumor-infiltrating lymphocytes (TILs), when present, are either dysfunctional or terminally exhausted. However, after checkpoint blockade therapy, it was possible to observe specific recruitment of adaptive immune cells and an efficient systemic immune response. In this review article, we attempt to address current knowledge regarding the tumor and immune microenvironment in rGBM. Furthermore, immunosuppression induced by GAMs and TIL dysfunction was revisited to account for genetic defects that can determine resistance to therapies and manipulate the immune microenvironment upon recurrence. Accordingly, we reevaluated the microenvironment of some of our rGBM patients treated with dendritic cell immunotherapy, with the goal of identifying predictive immune indicators of better treatment response. |
| first_indexed | 2024-03-10T04:31:37Z |
| format | Article |
| id | doaj.art-3dacdac4d0ed48af99deae8e3526a6da |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:31:37Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3dacdac4d0ed48af99deae8e3526a6da2023-11-23T04:04:25ZengMDPI AGCancers2072-66942021-12-011324615610.3390/cancers13246156Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic ApproachesElena Anghileri0Monica Patanè1Natalia Di Ianni2Irene Sambruni3Martina Maffezzini4Micaela Milani5Luisa Maddaloni6Bianca Pollo7Marica Eoli8Serena Pellegatta9Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, ItalyThe interpretation of the presence and function of immune infiltration in glioblastoma (GBM) is still debated. Over the years, GBM has been considered a cold tumor that is less infiltrated by effector cells and characterized by a high proportion of immunosuppressive innate immune cells, including GBM-associated microglia/macrophages (GAMs). In this context, the failure of checkpoint inhibitors, particularly in recurrent GBM (rGBM), caused us to look beyond the clinical results and consider the point of view of immune cells. The tumor microenvironment in rGBM can be particularly hostile, even when exposed to standard immunomodulatory therapies, and tumor-infiltrating lymphocytes (TILs), when present, are either dysfunctional or terminally exhausted. However, after checkpoint blockade therapy, it was possible to observe specific recruitment of adaptive immune cells and an efficient systemic immune response. In this review article, we attempt to address current knowledge regarding the tumor and immune microenvironment in rGBM. Furthermore, immunosuppression induced by GAMs and TIL dysfunction was revisited to account for genetic defects that can determine resistance to therapies and manipulate the immune microenvironment upon recurrence. Accordingly, we reevaluated the microenvironment of some of our rGBM patients treated with dendritic cell immunotherapy, with the goal of identifying predictive immune indicators of better treatment response.https://www.mdpi.com/2072-6694/13/24/6156glioblastomarecurrencetumor microenvironmenttumor infiltrating lymphocytesdysfunctionimmunotherapy |
| spellingShingle | Elena Anghileri Monica Patanè Natalia Di Ianni Irene Sambruni Martina Maffezzini Micaela Milani Luisa Maddaloni Bianca Pollo Marica Eoli Serena Pellegatta Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches Cancers glioblastoma recurrence tumor microenvironment tumor infiltrating lymphocytes dysfunction immunotherapy |
| title | Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches |
| title_full | Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches |
| title_fullStr | Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches |
| title_full_unstemmed | Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches |
| title_short | Deciphering the Labyrinthine System of the Immune Microenvironment in Recurrent Glioblastoma: Recent Original Advances and Lessons from Clinical Immunotherapeutic Approaches |
| title_sort | deciphering the labyrinthine system of the immune microenvironment in recurrent glioblastoma recent original advances and lessons from clinical immunotherapeutic approaches |
| topic | glioblastoma recurrence tumor microenvironment tumor infiltrating lymphocytes dysfunction immunotherapy |
| url | https://www.mdpi.com/2072-6694/13/24/6156 |
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