Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment
The composition of the tumor immune microenvironment has become a major determinant of response to therapy, particularly immunotherapy. Clinically, a tumor microenvironment lacking lymphocytes, so-called ''cold'' tumors, are considered poor candidates for immune checkpoint inhibi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000430 |
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| author | Lin Ma Jian-Hua Mao Mary Helen Barcellos-Hoff |
| author_facet | Lin Ma Jian-Hua Mao Mary Helen Barcellos-Hoff |
| author_sort | Lin Ma |
| collection | DOAJ |
| description | The composition of the tumor immune microenvironment has become a major determinant of response to therapy, particularly immunotherapy. Clinically, a tumor microenvironment lacking lymphocytes, so-called ''cold'' tumors, are considered poor candidates for immune checkpoint inhibition. In this review, we describe the diversity of the tumor immune microenvironment in breast cancer and how radiation exposure alters carcinogenesis. We review the development and use of a radiation-genetic mammary chimera model to clarify the mechanism by which radiation acts. Using the chimera model, we demonstrate that systemic inflammation elicited by a low dose of radiation is key to the construction of an immunosuppressive tumor microenvironment, resulting in aggressive, rapidly growing tumors lacking lymphocytes. Our experimental studies inform the non-mutagenic mechanisms by which radiation affects cancer and provide insight into the genesis of cold tumors. |
| format | Article |
| id | doaj-art-e868adf53ee04729893bef08004f3a06 |
| institution | OA Journals |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-e868adf53ee04729893bef08004f3a062025-08-20T02:24:45ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-06-016410116410.1016/j.neo.2025.101164Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironmentLin Ma0Jian-Hua Mao1Mary Helen Barcellos-Hoff2Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, ChinaBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USADepartment of Radiation Oncology, School of Medicine, Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143 USA; Corresponding author.The composition of the tumor immune microenvironment has become a major determinant of response to therapy, particularly immunotherapy. Clinically, a tumor microenvironment lacking lymphocytes, so-called ''cold'' tumors, are considered poor candidates for immune checkpoint inhibition. In this review, we describe the diversity of the tumor immune microenvironment in breast cancer and how radiation exposure alters carcinogenesis. We review the development and use of a radiation-genetic mammary chimera model to clarify the mechanism by which radiation acts. Using the chimera model, we demonstrate that systemic inflammation elicited by a low dose of radiation is key to the construction of an immunosuppressive tumor microenvironment, resulting in aggressive, rapidly growing tumors lacking lymphocytes. Our experimental studies inform the non-mutagenic mechanisms by which radiation affects cancer and provide insight into the genesis of cold tumors.http://www.sciencedirect.com/science/article/pii/S1476558625000430Tumor microenvironmentRadiation carcinogenesisTGFβDNA damage responseImmunophenotypeEvolution |
| spellingShingle | Lin Ma Jian-Hua Mao Mary Helen Barcellos-Hoff Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment Neoplasia: An International Journal for Oncology Research Tumor microenvironment Radiation carcinogenesis TGFβ DNA damage response Immunophenotype Evolution |
| title | Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| title_full | Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| title_fullStr | Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| title_full_unstemmed | Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| title_short | Systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| title_sort | systemic inflammation in response to radiation drives the genesis of an immunosuppressed tumor microenvironment |
| topic | Tumor microenvironment Radiation carcinogenesis TGFβ DNA damage response Immunophenotype Evolution |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000430 |
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