A ‘Hybrid’ Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. HDRT + LDRT in Stimulating Anti-Tumor Immunity: A Preclinical Snapshot
3. Immunobiology Mechanisms of HDRT + LDRT
3.1. HDRT: A Powerful Tool to Inspire Anti-Tumor Immunity
3.2. LDRT: An Immune Modulator
4. Clinical Challenges: How Will We Bridge the Gap between Theory and Practice?
4.1. How to Decide the Number of HDRT Site
4.2. Target Volume of HDRT
4.3. The Impact of Patients’ Immune Function
5. Clinical Decision Suggestions
5.1. Single Tumor Site
5.2. Oligo-Metastasis (OGM) Tumor
5.3. Polymetastatic Disease/High Tumor Burden
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Authors | Mice and Cell Line | Number of Tumor Sites | RT Regimen | Immunotherapy | Results |
---|---|---|---|---|---|
H Barsoumian et al. [19] | 129Sv/Ev mice 344SQ parental lung adenocarcinoma cell line | 2 | 12 Gy*3 HDRT to the primary tumor + 1 Gy*2 LDRT to the secondary tumor (3 days after HDRT) | anti-CTLA-4 anti-PD1 | Delayed growth in both primary and secondary tumors. Enhanced natural killer cell activation, increased M1 macrophages and CD4 + T-cells, and decreased TGF-β in secondary tumors. |
H Barsoumian et al. [20] | 129Sv/Ev mice 344SQ parental lung adenocarcinoma cell line | 2 | 12 Gy*3 HDRT to the primary tumor + 1 Gy*2 LDRT to the secondary tumor (3 days after HDRT) | anti-TIGIT anti-PD1 | Delayed growth in both primary and secondary tumors, reduced the exhaustion of T-cells, generated effector immune memory, and prolonged survival. |
Y Hu et al. [25] | 129Sv/Ev mice 344SQ parental lung adenocarcinoma cell line | 2 | 12 Gy*3 HDRT to the primary tumor + 1 Gy*2 LDRT to the secondary tumor (3 days after HDRT) | anti-PD1 anti-CTLA4 NBTXR3 nanoparticle | Slowed the growth of both primary and secondary tumors, suppressed the appearance of lung metastases, increased survival rates, induced robust long-term immune memory, and increased the CD8/Treg ratio in the secondary tumors |
T Savage et al. [26] | C57BL/6 mice Lewis Lung Carcinoma, 3LL | 1 | 22 Gy*1 + 0.5 Gy*4(12 days after HDRT) to the tumor site | - | Delayed tumor growth, increased survival, reduced Tregs and M2 macrophages in the tumor microenvironment (TME), and increased systemic T-cell responses. |
BalB/C mice breast carcinoma cell line, 4T1 | 1 | 22 Gy*1 to the tumor site + 0.5 Gy*4(12 days after HDRT) to the whole lung (metastatic prone organ) | - | Delayed local tumor progression, suppressed pulmonary metastases, remodeled the metastatic niche with decreased Tregs and increased effector T-cell infiltration in lungs, and increased survival. | |
J Liu et al. [16] | BALB/C mice mammary carcinoma 4T1 and colon carcinoma CT26 cell lines | 2 | 0.1 Gy total body irradiation (3 days before HDRT) + 8 Gy*3 to the primary tumor | - | Delayed growth in both primary and secondary tumors, increased secondary tumor infiltration of CD8+ T-Cells, decreased myeloid-derived suppressor cells (MDSCs) and M2 macrophages in the secondary tumor, and inhibited metastasis |
R Patel et al. [27] | C57Bl/6 and BALB/c mice B78 melanoma tumors cell line | 2 | targeted radionuclide therapy (TRT) using 50uCi90Y-NM600 (2.5 Gy) + 12 Gy external beam radiotherapy targeting the primary tumor | anti-CTLA4 | Improved tumor response at the secondary tumor not targeted by EBRT and improved overall survival, augmented response to ICIs, and induced robust long-term immune memory. |
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Ji, H.; Zhou, Z. A ‘Hybrid’ Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy. Cancers 2022, 14, 3505. https://doi.org/10.3390/cancers14143505
Ji H, Zhou Z. A ‘Hybrid’ Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy. Cancers. 2022; 14(14):3505. https://doi.org/10.3390/cancers14143505
Chicago/Turabian StyleJi, Hongshan, and Zhiguo Zhou. 2022. "A ‘Hybrid’ Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy" Cancers 14, no. 14: 3505. https://doi.org/10.3390/cancers14143505