# Radiotherapy Combined with Immune Checkpoint Inhibitor on Murine Fibrosarcoma and a Narrative Review of Clinical Studies

## TL;DR

This study shows that combining radiotherapy with an immune checkpoint inhibitor can significantly delay tumor growth in mice and may be a promising treatment for soft tissue sarcoma.

## Contribution

The study demonstrates a synergistic effect of combining an immune checkpoint inhibitor with radiotherapy in murine fibrosarcoma and reviews limited clinical evidence for this approach in soft tissue sarcoma.

## Key findings

- The combination group showed the most significant tumor growth delay and increased apoptosis.
- The combination treatment led to higher immune cell activation (CD4+, CD8+, and IFN-γ).
- Clinical data on combined ICI and RT for soft tissue sarcoma is limited but suggests potential synergism with acceptable toxicity.

## Abstract

Purpose: The objective of this study was to evaluate the synergistic effect of combining an immune checkpoint inhibitor (ICI) with radiotherapy (RT) on murine fibrosarcoma and to conduct a narrative review of clinical studies on soft tissue sarcoma (STS). Materials and Methods: Forty male C3H mice (aged 5 weeks) were injected intramuscularly with 2 × 105 FSaII cells into the right thigh and randomly assigned to four groups: (1) control; (2) RT; (3) InVivoMab™ (CD279) (mouse anti-PD-1 antibody) (ICI group); and (4) combined treatment with InVivoMab™ (CD279) and RT (combination group). On day −1, ICI was administered intraperitoneally. On day 0, RT (10 Gy, single fraction) was delivered locally to the tumors in the right hind limb. Subsequently, ICI was injected twice weekly (a total of 8 times). On day 26, all mice were euthanized, and the results were analyzed. In addition, a narrative review was conducted to identify clinical evidence. Results: On day 26, mean gross tumor volumes were 3578.13 ± 407.32 mm3 in the control group, 1995.72 ± 970.46 mm3 in the RT group, 2729.96 ± 286.47 mm3 in the ICI group, and 1007.92 ± 197.36 mm3 in the combination group. Gross tumor growth delay was most pronounced in the combination group. Moreover, the TUNEL assay demonstrated a significant increase in apoptosis in the combination group. Analysis of the underlying immune system revealed significantly higher expression of CD4+, CD8+, and IFN-γ in the combination group. The literature search identified only 12 case reports and 3 prospective studies involving patients with STS treated with the combined treatment of ICI and RT, suggesting potential synergism with acceptable toxicity. Conclusions: The current study demonstrated a synergistic effect of combining an ICI with RT in murine fibrosarcoma. There was limited data in the clinical setting. Further investigations are warranted to determine the optimal combination strategy of ICI and RT for STS.