Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations
Abstract Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent che...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01139-8 |
| _version_ | 1797817866441981952 |
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| author | Leilei Wu Zhenshan Zhang Menglin Bai Yujie Yan Jinming Yu Yaping Xu |
| author_facet | Leilei Wu Zhenshan Zhang Menglin Bai Yujie Yan Jinming Yu Yaping Xu |
| author_sort | Leilei Wu |
| collection | DOAJ |
| description | Abstract Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent chemoradiotherapy has been the standard of care since the PACIFIC trial. Preclinical evidence has demonstrated the role of RT in the cancer-immune cycle and the synergistic effect of RT combined with ICIs (iRT). However, RT exerts a double-edged effect on immunity and the combination strategy still could be optimized in many areas. In the context of LA-NSCLC, optimized RT modality, choice, timing, and duration of ICIs, care for oncogenic addicted tumors, patient selection, and novel combination strategies require further investigation. Targeting these blind spots, novel approaches are being investigated to cross the borders of PACIFIC. We discussed the development history of iRT and summarized the updated rationale for the synergistic effect. We then summarized the available research data on the efficacy and toxicity of iRT in LA-NSCLC for cross-trial comparisons to eliminate barriers. Progression during and after ICIs consolidation therapy has been regarded as a distinct resistance scenario from primary or secondary resistance to ICIs, the subsequent management of which has also been discussed. Finally, based on unmet needs, we probed into the challenges, strategies, and auspicious orientations to optimize iRT in LA-NSCLC. In this review, we focus on the underlying mechanisms and recent advances of iRT with an emphasis on future challenges and directions that warrant further investigation. Taken together, iRT is a proven and potential strategy in LA-NSCLC, with multiple promising approaches to further improve the efficacy. Video Abstract |
| first_indexed | 2024-03-13T08:59:46Z |
| format | Article |
| id | doaj.art-bab73e89d44a413a8ceab9cf67e9cd4e |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-13T08:59:46Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-bab73e89d44a413a8ceab9cf67e9cd4e2023-05-28T11:23:04ZengBMCCell Communication and Signaling1478-811X2023-05-0121112810.1186/s12964-023-01139-8Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientationsLeilei Wu0Zhenshan Zhang1Menglin Bai2Yujie Yan3Jinming Yu4Yaping Xu5Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Radiation Oncology, Fudan University Shanghai Cancer CenterDepartment of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of MedicineAbstract Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent chemoradiotherapy has been the standard of care since the PACIFIC trial. Preclinical evidence has demonstrated the role of RT in the cancer-immune cycle and the synergistic effect of RT combined with ICIs (iRT). However, RT exerts a double-edged effect on immunity and the combination strategy still could be optimized in many areas. In the context of LA-NSCLC, optimized RT modality, choice, timing, and duration of ICIs, care for oncogenic addicted tumors, patient selection, and novel combination strategies require further investigation. Targeting these blind spots, novel approaches are being investigated to cross the borders of PACIFIC. We discussed the development history of iRT and summarized the updated rationale for the synergistic effect. We then summarized the available research data on the efficacy and toxicity of iRT in LA-NSCLC for cross-trial comparisons to eliminate barriers. Progression during and after ICIs consolidation therapy has been regarded as a distinct resistance scenario from primary or secondary resistance to ICIs, the subsequent management of which has also been discussed. Finally, based on unmet needs, we probed into the challenges, strategies, and auspicious orientations to optimize iRT in LA-NSCLC. In this review, we focus on the underlying mechanisms and recent advances of iRT with an emphasis on future challenges and directions that warrant further investigation. Taken together, iRT is a proven and potential strategy in LA-NSCLC, with multiple promising approaches to further improve the efficacy. Video Abstracthttps://doi.org/10.1186/s12964-023-01139-8Locally advanced non-small cell lung cancer (LA-NSCLC)RadiotherapyImmune checkpoint inhibitors (ICIs)RT combined with ICIs (iRT)AdvancesChallenges |
| spellingShingle | Leilei Wu Zhenshan Zhang Menglin Bai Yujie Yan Jinming Yu Yaping Xu Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations Cell Communication and Signaling Locally advanced non-small cell lung cancer (LA-NSCLC) Radiotherapy Immune checkpoint inhibitors (ICIs) RT combined with ICIs (iRT) Advances Challenges |
| title | Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations |
| title_full | Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations |
| title_fullStr | Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations |
| title_full_unstemmed | Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations |
| title_short | Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations |
| title_sort | radiation combined with immune checkpoint inhibitors for unresectable locally advanced non small cell lung cancer synergistic mechanisms current state challenges and orientations |
| topic | Locally advanced non-small cell lung cancer (LA-NSCLC) Radiotherapy Immune checkpoint inhibitors (ICIs) RT combined with ICIs (iRT) Advances Challenges |
| url | https://doi.org/10.1186/s12964-023-01139-8 |
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