Investigation of endogenous and adoptively transferred T cell function in a genetic mouse model of lung adenocarcinoma

The clinical success of immune checkpoint blockade, including in patients with lung cancer, has clearly demonstrated that the body's immune system is capable of tumor cytotoxicity if modulated appropriately. Unfortunately, only a minority of patients with solid tumors respond to checkpoint blockade, and even fewer respond to other immunotherapeutic modalities like adoptive cell therapy (ACT). The reasons for these low response rates are not well understood, suggesting an improved understanding of the mechanisms which shape a tumor immune response and promote T cell dysfunction is needed. Toward these ends, we first sought to characterize the transcriptional changes leading to toward dysfunction in endogenous T cell responses. Using an autochthonous mouse model of lung adenocarcinoma, we longitudinally profiled CD8⁺ T cells from the lungs of tumor bearing mice using single cell RNAseq (scRNAseq).

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Canner, David(David Allen)

Advisor dc:contributor.advisor

• Tyler Jacks.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/121878

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/121878