Low-dose Radiation Improves Tumor Immune Microenvironment, Enhancing the Effects of Anti-CTLA-4 Therapy

Radiotherapy destroys tumor cells primarily through direct DNA damage by high-energy particles or indirect DNA damage by free radicals. High-dose radiotherapy (HDR) destroys tumor cells while also damaging normal cells and may potentially cause immunosuppression. The effect of low-dose radiotherapy...

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Vydáno v:Iranian journal of immunology Ročník 22; číslo 1; s. 47
Hlavní autoři: Dong, Jigang, Qi, Ying, Sha, Sha
Médium: Journal Article
Jazyk:angličtina
Vydáno: Iran Shiraz Institute for Cancer Research 01.03.2025
Témata:
Animals
Cancer therapies
CD8 antigen
Cell Line, Tumor
Chemokines
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 Antigen - immunology
CTLA-4 protein
CXCL10 protein
CXCL11 protein
Cytokines - metabolism
Disease Models, Animal
DNA damage
Female
Flow cytometry
Free radicals
Humans
Immune checkpoint inhibitors
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Immune response
Immune system
Immunosuppression
Interferon
Lung cancer
Lung Neoplasms - immunology
Lung Neoplasms - pathology
Lung Neoplasms - radiotherapy
Lung Neoplasms - therapy
Lymphocytes
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - immunology
Mice
Radiation therapy
Tumor cells
Tumor microenvironment
Tumor Microenvironment - immunology
Tumor Microenvironment - radiation effects
Tumors
Iran
United States > US
China
Low-dose radiotherapy
Tumor immune microenvironment
Interferon
Anti-CTLA-4
ISSN:1735-1383, 1735-367X, 1735-367X
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Shrnutí:Radiotherapy destroys tumor cells primarily through direct DNA damage by high-energy particles or indirect DNA damage by free radicals. High-dose radiotherapy (HDR) destroys tumor cells while also damaging normal cells and may potentially cause immunosuppression. The effect of low-dose radiotherapy (LDR) on the tumor microenvironment (TME) may differ from those of HDR. To determine if combining low-dose radiotherapy with immune checkpoint inhibitors results in synergistic effects. We established a mouse model for lung cancer and categorized mice into 4 cohorts: NC (negative control) cohort, LDR cohort, anti-CTLA-4 cohort, and LDR+anti-CTLA-4 cohort. Changes in tumor volume were observed in each group, with particular attention given to the variations in immune cells and cytokines within the mouse tumors following LDR. The mice in the LDR+anti-CTLA-4 group exhibited the slowest growth in tumor volume, and low-dose radiotherapy tended to inhibit tumor growth. The proportion of infiltrating CD8+T cells increased and the proportion of infiltrating Treg cells decreased in the tumor after LDR. The levels of interferon (IFN) and the chemokines CXCL9, CXCL10 and CXCL11 were increased after low-dose radiotherapy. LDR has the ability to alter the immune microenvironment of tumors by promoting the production of IFN. Additionally, when combined with anti-CTLA-4, whole-body LDR can effectively suppress tumor growth in mice. The finding is of potential clinical significance and deserves further exploration.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1735-1383
1735-367X
1735-367X
DOI:10.22034/iji.2025.103258.2825