Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice
In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cel...
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3894 |
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| author | Seon-Hee Kim Eun Mi Go Dong Hoon Shin Beom K. Choi Chungyong Han |
| author_facet | Seon-Hee Kim Eun Mi Go Dong Hoon Shin Beom K. Choi Chungyong Han |
| author_sort | Seon-Hee Kim |
| collection | DOAJ |
| description | In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological factors involved in a conditioning regimen is important to design effective strategies in ACT. Here, by using an ACT model of murine melanoma, we evaluate the effect of the total body irradiation (TBI) and interleukin-2 (IL-2) treatment combination. The use of a <i>Rag1</i> knock-out strain, which lacks endogenous T cells, enables the identification of factors in a way that focuses more on transferred T cells. We demonstrate that the TBI/IL-2 combination has no additive effect in ACT, although each conditioning improves the therapeutic outcome. While the combination increases the frequency of transferred T cells in lymphoid and tumor tissues, the activation intensity of the cells is reduced compared to that of the sole TBI treatment. Notably, we show that in the presence of TBI, the IL-2 treatment reduces the frequency of intra-tumoral dendritic cells, which are crucial for T cell activation. The current study provides insights into the immunological events involved in the TBI/IL-2 combination in ACT. |
| first_indexed | 2024-03-09T17:50:49Z |
| format | Article |
| id | doaj.art-daca389f90da491ab7fda84b61f2239e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:49Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-daca389f90da491ab7fda84b61f2239e2023-11-24T10:45:35ZengMDPI AGCells2073-44092022-12-011123389410.3390/cells11233894Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out MiceSeon-Hee Kim0Eun Mi Go1Dong Hoon Shin2Beom K. Choi3Chungyong Han4Immuno-Oncology Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaImmuno-Oncology Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaTargeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaBiomedicine Production Branch, Cancer Immunotherapy Working Group, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaImmuno-Oncology Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaIn adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological factors involved in a conditioning regimen is important to design effective strategies in ACT. Here, by using an ACT model of murine melanoma, we evaluate the effect of the total body irradiation (TBI) and interleukin-2 (IL-2) treatment combination. The use of a <i>Rag1</i> knock-out strain, which lacks endogenous T cells, enables the identification of factors in a way that focuses more on transferred T cells. We demonstrate that the TBI/IL-2 combination has no additive effect in ACT, although each conditioning improves the therapeutic outcome. While the combination increases the frequency of transferred T cells in lymphoid and tumor tissues, the activation intensity of the cells is reduced compared to that of the sole TBI treatment. Notably, we show that in the presence of TBI, the IL-2 treatment reduces the frequency of intra-tumoral dendritic cells, which are crucial for T cell activation. The current study provides insights into the immunological events involved in the TBI/IL-2 combination in ACT.https://www.mdpi.com/2073-4409/11/23/3894adoptive T cell therapytotal body irradiationinterleukin-2melanoma<i>Rag1</i> knock-out micedendritic cell |
| spellingShingle | Seon-Hee Kim Eun Mi Go Dong Hoon Shin Beom K. Choi Chungyong Han Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice Cells adoptive T cell therapy total body irradiation interleukin-2 melanoma <i>Rag1</i> knock-out mice dendritic cell |
| title | Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice |
| title_full | Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice |
| title_fullStr | Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice |
| title_full_unstemmed | Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice |
| title_short | Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing <i>Rag1</i> Knock-Out Mice |
| title_sort | pro and anti tumoral factors involved in total body irradiation and interleukin 2 conditioning in adoptive t cell therapy of melanoma bearing i rag1 i knock out mice |
| topic | adoptive T cell therapy total body irradiation interleukin-2 melanoma <i>Rag1</i> knock-out mice dendritic cell |
| url | https://www.mdpi.com/2073-4409/11/23/3894 |
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