Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer
Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechani...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3197 |
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| author | Gaber Plavc Tanja Jesenko Miha Oražem Primož Strojan |
| author_facet | Gaber Plavc Tanja Jesenko Miha Oražem Primož Strojan |
| author_sort | Gaber Plavc |
| collection | DOAJ |
| description | Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC. |
| first_indexed | 2024-03-10T15:13:25Z |
| format | Article |
| id | doaj.art-e75cec7efe2d4ab29d5b0cc8ec71888d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:13:25Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e75cec7efe2d4ab29d5b0cc8ec71888d2023-11-20T19:10:55ZengMDPI AGCancers2072-66942020-10-011211319710.3390/cancers12113197Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck CancerGaber Plavc0Tanja Jesenko1Miha Oražem2Primož Strojan3Department of Radiation Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaDepartment of Radiation Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, SloveniaDepartment of Radiation Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, SloveniaImmunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC.https://www.mdpi.com/2072-6694/12/11/3197head and neck neoplasmsimmunoradiotherapySBRTimmunotherapyabscopal effect |
| spellingShingle | Gaber Plavc Tanja Jesenko Miha Oražem Primož Strojan Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer Cancers head and neck neoplasms immunoradiotherapy SBRT immunotherapy abscopal effect |
| title | Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer |
| title_full | Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer |
| title_fullStr | Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer |
| title_full_unstemmed | Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer |
| title_short | Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer |
| title_sort | challenges in combining immunotherapy with radiotherapy in recurrent metastatic head and neck cancer |
| topic | head and neck neoplasms immunoradiotherapy SBRT immunotherapy abscopal effect |
| url | https://www.mdpi.com/2072-6694/12/11/3197 |
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