CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer
University of California, Los Angeles · VA Greater Los Angeles Healthcare System
Abstract
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as…
Citation impact
- FWCI
- 27.07
- Percentile
- 100%
- References
- 71
Authors
16- RJRaymond J. Lim
University of California, Los Angeles
- RSRamin Salehi‐Rad
University of California, Los Angeles, VA Greater Los Angeles Healthcare System
- LMLinh M. Tran
University of California, Los Angeles, VA Greater Los Angeles Healthcare System
- MSMichael S. Oh
University of California, Los Angeles
- CDCamelia Dumitras
University of California, Los Angeles
Topics & keywords
- CXCL9
- T cell
- Tumor microenvironment
- Immune checkpoint
- Cancer research
- Immune system
- Dendritic cell
- Cancer immunotherapy
- Good health and well-being
Funding
- UDU.S. Department of Veterans Affairs
- TDTobacco-Related Disease Research ProgramAward: T30DT0963
- BLBiomedical Laboratory Research and Development, VA Office of Research and DevelopmentAward: 1lK2BX006194-01
- NINational Institutes of HealthAwards: HL072752, CA-16042, 5P30 AI-28697, AI-28697, P30 CA-16042
- UOUniversity of California, Los Angeles
- NHNational Heart, Lung, and Blood InstituteAwards: T32-HL072752, P30 CA-16042
- JCJonsson Comprehensive Cancer Center
- DGDavid Geffen School of Medicine, University of California, Los Angeles