Radiat Oncol J.  2023 Jun;41(2):129-139. 10.3857/roj.2023.00185.

Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect

• Zheng Y
• Liu X
• Li N
• Zhao A
• Sun Z
• Wang M
• Luo J

• KMID: 2544027
• DOI: http://doi.org/10.3857/roj.2023.00185

Abstract

Purpose
To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes.
Materials and Methods
Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration.
Results
We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis.
Conclusion
Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.

Keyword

Melanoma; Abscopal effect; Radiotherapy; Anti-PD-1; Immune cells; RNA sequencing