000043577 001__ 43577 000043577 005__ 20240823145748.0 000043577 0247_ $$2doi$$a10.6083/bpxhc43577 000043577 037__ $$aIR 000043577 041__ $$aeng 000043577 245__ $$aIdentification of cellular interactions in the tumor immune microenvironment underlying CD8 T cell exhaustion 000043577 260__ $$bOregon Health and Science University 000043577 269__ $$a2024 000043577 336__ $$aAbstract 000043577 520__ $$aImmune checkpoint inhibitors have shown success in treating a subset of patients with certain late-stage cancers. However, these treatments fail in many other patients, due to mechanisms that have yet to be fully characterized. The process of T cell exhaustion, by which T cells become dysfunctional in response to extended exposure to antigen, has been implicated in immunotherapy resistance. Single-cell RNA sequencing (scRNA-seq) produces an abundance of data to analyze this process, facilitating insights into cellular processes related to treatment efficacy. However, due to the complexity of the process, contributions of other cell types to a process within a single cell type cannot be simply inferred. These results demonstrate that our analysis framework can identify potential mechanisms driving key cellular processes implicated in the failure of cancer immune checkpoint inhibitors. The framework can be applied to all cell types in the tumor immune microenvironment, expanding our understanding of key biological processes that underpin the effective treatment of cancer. 000043577 540__ $$fCC BY 000043577 542__ $$fIn copyright - joint owners 000043577 650__ $$aComputational Biology$$031511 000043577 650__ $$aImmunotherapy$$020724 000043577 650__ $$aSequence Analysis, RNA$$029959 000043577 650__ $$aGene Regulatory Networks$$037326 000043577 650__ $$aT-Cell Exhaustion$$013992 000043577 650__ $$aCD8-Positive T-Lymphocytes$$030782 000043577 6531_ $$abioinformatics 000043577 6531_ $$acancer immunology 000043577 6531_ $$ascRNA-seq 000043577 691__ $$aSchool of Medicine$$041369 000043577 692__ $$aDepartment of Medical Informatics and Clinical Epidemiology$$041422 000043577 7001_ $$aKlocke, Christopher$$uOregon Health and Science University$$041354 000043577 7001_ $$aMoran, Amy E.$$uOregon Health and Science University$$041354 000043577 7001_ $$aAdey, Andrew C.$$uOregon Health and Science University$$041354 000043577 7001_ $$aMcWeeney, Shannon K.$$uOregon Health and Science University$$041354 000043577 7001_ $$aWu, Guanming$$uOregon Health and Science University$$041354 000043577 711__ $$aResearch Week$$uOregon Health and Science University$$d2024 000043577 8564_ $$98914d82d-7953-48e0-9633-6fdb8edda6d4$$s100395$$uhttps://digitalcollections.ohsu.edu/record/43577/files/ResearchWeek.2024.Klocke.Christopher.pdf 000043577 980__ $$aResearch Week