Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model
Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as t...
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| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10476 |
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| author | Haa-Na Song Hana Jin Jung-Hoon Kim In-Bong Ha Ki-Mun Kang Hoon-Sik Choi Ho-Jin Jeong Min-Young Kim Hye-Jung Kim Bae-Kwon Jeong |
| author_facet | Haa-Na Song Hana Jin Jung-Hoon Kim In-Bong Ha Ki-Mun Kang Hoon-Sik Choi Ho-Jin Jeong Min-Young Kim Hye-Jung Kim Bae-Kwon Jeong |
| author_sort | Haa-Na Song |
| collection | DOAJ |
| description | Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:38Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2d24d89961ea4de7b9f1e1e68bcf955a2023-11-22T16:10:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191047610.3390/ijms221910476Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma ModelHaa-Na Song0Hana Jin1Jung-Hoon Kim2In-Bong Ha3Ki-Mun Kang4Hoon-Sik Choi5Ho-Jin Jeong6Min-Young Kim7Hye-Jung Kim8Bae-Kwon Jeong9Division of Hemato-Oncology, Department of Internal Medicine, Gyeongsang National University of Medicine and Gyeongsang National University Hospital, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaDivision of Hemato-Oncology, Department of Internal Medicine, Gyeongsang National University of Medicine and Gyeongsang National University Hospital, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaDivision of Endocrinology, Department of Internal Medicine, Gyeongsang National University of Medicine and Gyeongsang National University Hospital, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaInstitute of Health Science, Gyeongsang National University, Jinju 52727, KoreaLocal radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.https://www.mdpi.com/1422-0067/22/19/10476abscopal effectradiotherapyimmune checkpoint inhibitortriple-negative breast cancer |
| spellingShingle | Haa-Na Song Hana Jin Jung-Hoon Kim In-Bong Ha Ki-Mun Kang Hoon-Sik Choi Ho-Jin Jeong Min-Young Kim Hye-Jung Kim Bae-Kwon Jeong Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model International Journal of Molecular Sciences abscopal effect radiotherapy immune checkpoint inhibitor triple-negative breast cancer |
| title | Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model |
| title_full | Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model |
| title_fullStr | Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model |
| title_full_unstemmed | Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model |
| title_short | Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model |
| title_sort | abscopal effect of radiotherapy enhanced with immune checkpoint inhibitors of triple negative breast cancer in 4t1 mammary carcinoma model |
| topic | abscopal effect radiotherapy immune checkpoint inhibitor triple-negative breast cancer |
| url | https://www.mdpi.com/1422-0067/22/19/10476 |
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