Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors
Summary: Immunotherapies are used as adjuvant therapies for cancers. However, knowledge of how traditional cancer treatments affect immunotherapies is limited. Using mouse models, we demonstrate that tumor-draining lymph nodes (TdLNs) are critical for tumor antigen-specific T cell response. However,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220302418 |
| _version_ | 1818457149903208448 |
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| author | Xianda Zhao Beminet Kassaye Dechen Wangmo Emil Lou Subbaya Subramanian |
| author_facet | Xianda Zhao Beminet Kassaye Dechen Wangmo Emil Lou Subbaya Subramanian |
| author_sort | Xianda Zhao |
| collection | DOAJ |
| description | Summary: Immunotherapies are used as adjuvant therapies for cancers. However, knowledge of how traditional cancer treatments affect immunotherapies is limited. Using mouse models, we demonstrate that tumor-draining lymph nodes (TdLNs) are critical for tumor antigen-specific T cell response. However, removing TdLNs concurrently with established primary tumors did not affect the immune checkpoint blockade (ICB) response on localized secondary tumor due to immunotolerance in TdLNs and distribution of antigen-specific T cells in peripheral lymphatic organs. Notably, treatment response improved with sequential administration of 5-fluorouracil (5-FU) and ICB compared with concurrent administration of ICB with 5-FU. Immune profiling revealed that using 5-FU as induction treatment increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T cell depletion. We show that the effect of traditional cytotoxic treatment, not TdLNs, influences immunotherapy response in localized secondary tumors. We postulate essential considerations for successful immunotherapy strategies in clinical conditions. |
| first_indexed | 2024-12-14T22:37:59Z |
| format | Article |
| id | doaj.art-718b5eb3692d43bd92bf376a9c678974 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T22:37:59Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-718b5eb3692d43bd92bf376a9c6789742022-12-21T22:45:03ZengElsevieriScience2589-00422020-05-01235Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary TumorsXianda Zhao0Beminet Kassaye1Dechen Wangmo2Emil Lou3Subbaya Subramanian4Department of Surgery, University of Minnesota Medical School, 11-212 Moos Tower, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota Medical School, 11-212 Moos Tower, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota Medical School, 11-212 Moos Tower, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota Medical School, 11-212 Moos Tower, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Immunotherapies are used as adjuvant therapies for cancers. However, knowledge of how traditional cancer treatments affect immunotherapies is limited. Using mouse models, we demonstrate that tumor-draining lymph nodes (TdLNs) are critical for tumor antigen-specific T cell response. However, removing TdLNs concurrently with established primary tumors did not affect the immune checkpoint blockade (ICB) response on localized secondary tumor due to immunotolerance in TdLNs and distribution of antigen-specific T cells in peripheral lymphatic organs. Notably, treatment response improved with sequential administration of 5-fluorouracil (5-FU) and ICB compared with concurrent administration of ICB with 5-FU. Immune profiling revealed that using 5-FU as induction treatment increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T cell depletion. We show that the effect of traditional cytotoxic treatment, not TdLNs, influences immunotherapy response in localized secondary tumors. We postulate essential considerations for successful immunotherapy strategies in clinical conditions.http://www.sciencedirect.com/science/article/pii/S2589004220302418TherapyBiological SciencesImmune ResponseCancer |
| spellingShingle | Xianda Zhao Beminet Kassaye Dechen Wangmo Emil Lou Subbaya Subramanian Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors iScience Therapy Biological Sciences Immune Response Cancer |
| title | Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors |
| title_full | Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors |
| title_fullStr | Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors |
| title_full_unstemmed | Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors |
| title_short | Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors |
| title_sort | chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors |
| topic | Therapy Biological Sciences Immune Response Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220302418 |
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