Accession Number : AD1050596


Title :   Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets


Descriptive Note : Technical Report,15 Jul 2016,14 Jul 2017


Corporate Author : Childrens Hospital Boston United States


Personal Author(s) : Kim, Carla


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050596.pdf


Report Date : 01 Aug 2017


Pagination or Media Count : 15


Abstract : Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new treatment for SCC. In the Lkb1/Pten mouse model of SCC, the cancer stem cells (CSCs) have high expression of the immune evasion molecule PD-L1, a ligand for the PD1 molecule expressed on T-cells known to mediate T-cell suppression. Antibody therapy that effectively inhibits PD1/PD-L1 interactions has had exciting success in SCC patients, yet the specific cellular mechanisms of therapy efficacy or paths to resistance are unknown. Lkb1/Pten mice with established SCC detected by MRI were treated with anti-PD1 antibody. There was no significant difference in the rate the tumor growth between the two groups, indicating that this mouse model may be a good model of immunotherapy resistance. CSCs were isolated by FACS, quantified, and reserved for future RNA-Seq studies. Interestingly, mice that received PD-L1 treatment showed an increased number of CSCs. Gene expression profiling will be used to learn what pathways govern SCC CSCs. These studies will yield cogent design and deployment of clinical trials with the best rational combination of agents for these acquired resistant and non-responsive lung cancer patients.


Descriptors :   immunotherapy , cultured cells , clinical trials , gene expression , cell line , lung cancer , neoplasms , stem cells , epithelial cells , therapy , antibodies


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE