Table 1.
Evidence of the potential synergistic effect of RT in combination with CAR-T cells.
| Tumor model | Scheme | Mechanism | Reference |
|---|---|---|---|
| Preclinical evidence of RT as a TME altering therapy | |||
| Melanoma | 1 × 15Gy | RT-induced type I IFN promoted CXCL10 expression, leading to increased CD8+ T cell infiltration. | Lim et al (17), |
| Multiple models | 3 × 8Gy | RT activated the STING pathway and induced type I IFNs to recruit DC and CD8+ T cells. | Vanpouille-Box et. al (18), |
| Prostate cancer | 10 × 2Gy | RT remodeled the tumor vasculature and improved oxygenation. | Potiron et al. (19), |
| Non-small cell lung carcinoma | 1 × 18Gy and 3 × 6Gy | Irradiated CAF decreased the pro-tumorigenic potential that affected angiogenesis and tumor growth. | Grinde et al. (20), |
| Breast cancer | 3 × 8Gy | RT induced up-regulation of ICAM-1 to enhance both the activation and tumor infiltration of CD8+ T cells. | Zhao et al. (21), |
| Melanoma | 1 × 15Gy | RT-induced IFN-γ increased the VCAM-1 expression on tumor vasculature to facilitate T cell infiltration. | Lugade et al. (22), |
| Multiple models | 1 × 6Gy | Liver-directed RT eliminated immunosuppressive hepatic macrophages and increased T cell function in liver metastatic models. | Yu et al. (23), |
| Lung adenocarcinoma | 2 × 1Gy | RT induced M1 macrophage polarization and enhanced immune cell infiltration. | Barsoumian et al. (24), |
| Multiple models | 2 × 12.5Gy | RT downregulated the expression of VEGF to reduce the recruitment of MDSC into tumors. | Lan et al. (25), |
| Prostate cancer | 2 × 10Gy | RT induced CXCL9 expression, leading to increased CD8+ T cell infiltration. | Keam et al. (26), |
| Preclinical evidence of RT in combination with CAR-T cells | |||
| Glioblastoma | 1 × 5Gy | RT facilitated vasculature normalization to promote CAR-T cell extravasation in the TME. | Murty et al. 2020 (27) |
| Pancreatic cancer | 1 × 2Gy | RT sensitized antigen-negative tumor cells to TRAIL-dependent killing mediated by CAR-T cells. | DeSelm et al. 2018 (28) |
| Glioblastoma | 1 × 4Gy | RT boosted CAR-T cell activity (IFN-γ production) and upregulated CAR-targeted stress ligand. | Weiss et al. 2018 (29) |
| Clinical studies of RT in combination with CAR-T cells | |||
| Diffuse large B-cell lymphoma | 20 × 2Gy | RT was related to CAR-T cell expansion and therapeutic durability of CAR-T cell therapy. | NCT03196830 (30) |
| Multiple Myeloma | 5 × 4Gy | The synergistic abscopal effect induced by localized RT and CAR-T cells. | NCT03070327 (31) |