1. Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites.
- Author
-
Martin, Alexandra L., Powell, Chase, Nagy, Mate Z., Innamarato, Patrick, Powers, John, Nichols, Derek, Anadon, Carmen M., Chaurio, Ricardo A., Kim, Sungjune, Wang, Min-hsuan, Gong, Bing, Wang, Xianzhe, Scheutz, Thomas J., Antonia, Scott J., Conejo-Garcia, Jose R., and Perez, Bradford A.
- Subjects
- *
SMALL cell lung cancer , *T cells , *B cells , *TUMOR antigens , *ANTIGEN presentation - Abstract
Radiation therapy (RT) can prime and boost systemic anti-tumor effects via STING activation, resulting in enhanced tumor antigen presentation and antigen recognition by T cells. It is increasingly recognized that optimal anti-tumor immune responses benefit from coordinated cellular (T cell) and humoral (B cell) responses. However, the nature and functional relevance of the RT-induced immune response are controversial, beyond STING signaling, and agonistic interventions are lacking. Here, we show that B and CD4+ T cell accumulation at tumor beds in response to RT precedes the arrival of CD8+ T cells, and both cell types are absolutely required for abrogated tumor growth in non-irradiated tumors. Further, RT induces increased expression of 4-1BB (CD137) in both T and B cells; both in preclinical models and in a cohort of patients with small cell lung cancer treated with thoracic RT. Accordingly, the combination of RT and anti-41BB therapy leads to increased immune cell infiltration in the tumor microenvironment and significant abscopal effects. Thus, 4-1BB therapy enhances radiation-induced tumor-specific immune responses via coordinated B and T cell responses, thereby preventing malignant progression at unirradiated tumor sites. These findings provide a rationale for combining RT and 4-1bb therapy in future clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF