Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.
Radiother Oncol
; 194: 110213, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38458258
ABSTRACT
BACKGROUND AND PURPOSE:
Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells. MATERIALS ANDMETHODS:
Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model.RESULTS:
We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile.CONCLUSION:
Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
T-Lymphocytes
Limits:
Animals
Language:
En
Journal:
Radiother Oncol
Year:
2024
Document type:
Article