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Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

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Technical Report,15 Jul 2016,14 Jul 2017

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Childrens Hospital Boston United States

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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 Lkb1Pten 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 PD1PD-L1 interactions has had exciting success in SCC patients, yet the specific cellular mechanisms of therapy efficacy or paths to resistance are unknown. Lkb1Pten 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.

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  • Medicine and Medical Research

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