SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer
Abstract High-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells expre...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-06-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01472-4 |
| _version_ | 1797806866779078656 |
|---|---|
| author | Kai Ji Yuhan Zhang Shengpeng Jiang Lin Sun Baozhong Zhang Dongzhi Hu Jun Wang Lujun Zhao Ping Wang Zhen Tao |
| author_facet | Kai Ji Yuhan Zhang Shengpeng Jiang Lin Sun Baozhong Zhang Dongzhi Hu Jun Wang Lujun Zhao Ping Wang Zhen Tao |
| author_sort | Kai Ji |
| collection | DOAJ |
| description | Abstract High-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells express signal regulatory protein α (SIRPα) to inhibit phagocytosis by phagocytes in the tumor microenvironment (TME). We postulated that SIRPα blockade enhances HRT by alleviating the inhibitory action of SIRPα on phagocytes. We demonstrated that SIRPα on myeloid cells was upregulated in the TME after HRT. When SIRPα blockade was administered with HRT, we observed superior antitumor responses compared with anti-SIRPα or HRT alone. When anti-SIRPα was administered to local HRT, the TME could become a tumoricidal niche that was heavily infiltrated by activated CD8+ T cells, but with limited myeloid-derived suppressor cells and tumor-associated macrophages. While CD8+ T cells were required for the effectiveness of the anti-SIRPα + HRT combination. The triple therapy with anti-SIRPα + HRT + anti-PD-1 had superior antitumor responses compared with the combination of any two therapies and established a strong and long-lasting adaptive immunological memory. Collectively, SIRPα blockade provides a novel way to overcome HRT resistance in oligometastatic CRC patients. Our results herein provide a valuable cancer treatment strategy that has the potential to be translated into clinical practice. |
| first_indexed | 2024-03-13T06:13:52Z |
| format | Article |
| id | doaj.art-b6abb51ccf3f4b488494fccf39cfdc6b |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-13T06:13:52Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-b6abb51ccf3f4b488494fccf39cfdc6b2023-06-11T11:05:57ZengNature Publishing GroupCell Death Discovery2058-77162023-06-019111210.1038/s41420-023-01472-4SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancerKai Ji0Yuhan Zhang1Shengpeng Jiang2Lin Sun3Baozhong Zhang4Dongzhi Hu5Jun Wang6Lujun Zhao7Ping Wang8Zhen Tao9Department of Pain Relief, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for CancerAbstract High-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells express signal regulatory protein α (SIRPα) to inhibit phagocytosis by phagocytes in the tumor microenvironment (TME). We postulated that SIRPα blockade enhances HRT by alleviating the inhibitory action of SIRPα on phagocytes. We demonstrated that SIRPα on myeloid cells was upregulated in the TME after HRT. When SIRPα blockade was administered with HRT, we observed superior antitumor responses compared with anti-SIRPα or HRT alone. When anti-SIRPα was administered to local HRT, the TME could become a tumoricidal niche that was heavily infiltrated by activated CD8+ T cells, but with limited myeloid-derived suppressor cells and tumor-associated macrophages. While CD8+ T cells were required for the effectiveness of the anti-SIRPα + HRT combination. The triple therapy with anti-SIRPα + HRT + anti-PD-1 had superior antitumor responses compared with the combination of any two therapies and established a strong and long-lasting adaptive immunological memory. Collectively, SIRPα blockade provides a novel way to overcome HRT resistance in oligometastatic CRC patients. Our results herein provide a valuable cancer treatment strategy that has the potential to be translated into clinical practice.https://doi.org/10.1038/s41420-023-01472-4 |
| spellingShingle | Kai Ji Yuhan Zhang Shengpeng Jiang Lin Sun Baozhong Zhang Dongzhi Hu Jun Wang Lujun Zhao Ping Wang Zhen Tao SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer Cell Death Discovery |
| title | SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| title_full | SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| title_fullStr | SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| title_full_unstemmed | SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| title_short | SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| title_sort | sirpα blockade improves the antitumor immunity of radiotherapy in colorectal cancer |
| url | https://doi.org/10.1038/s41420-023-01472-4 |
| work_keys_str_mv | AT kaiji sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT yuhanzhang sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT shengpengjiang sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT linsun sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT baozhongzhang sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT dongzhihu sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT junwang sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT lujunzhao sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT pingwang sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer AT zhentao sirpablockadeimprovestheantitumorimmunityofradiotherapyincolorectalcancer |