{"doi":"10.1101/2020.05.20.087379","title":"<i>In vivo</i> CRISPR screening identifies Fli1 as a transcriptional safeguard that restrains effector CD8 T cell differentiation during infection and cancer","abstract":"Summary Improving effector activity of antigen specific T cells is a major goal in cancer immunotherapy. Despite the identification of several effector T cell (T EFF )-driving transcription factors (TF), the transcriptional coordination of T EFF biology remains poorly understood. We developed an in vivo T cell CRISPR screening platform and identified a novel mechanism restraining T EFF biology through the ETS family TF, Fli1. Genetic deletion of Fli1 enhanced T EFF responses without compromising memory or exhaustion precursors. Fli1 restrained T EFF lineage differentiation by binding to cis -regulatory elements of effector-associated genes. Loss of Fli1 increased chromatin accessibility at ETS:RUNX motifs allowing more efficient Runx3-driven T EFF biology. CD8 T cells lacking Fli1 provided substantially better protection against multiple infections and tumors. These data indicate that Fli1 safeguards the developing CD8 T cell transcriptional landscape from excessive ETS:RUNX-driven T EFF cell differentiation. Moreover, genetic deletion of Fli1 improves T EFF differentiation and protective immunity in infections and cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123690,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556178,"name":"Eri Arai","orcid":"0000-0002-0076-4823","position":1,"is_corresponding":false},{"id":567064,"name":"Omar Khan","orcid":"0000-0002-7641-6163","position":2,"is_corresponding":false},{"id":567065,"name":"Zhen Zhang","orcid":"0000-0002-1840-3110","position":3,"is_corresponding":false},{"id":265861,"name":"Shin Foong Ngiow","orcid":"0000-0002-5738-2834","position":4,"is_corresponding":false},{"id":29306,"name":"Yuan He","orcid":"0000-0002-6461-5341","position":5,"is_corresponding":false},{"id":567066,"name":"Hua Huang","orcid":"0000-0002-8936-3371","position":6,"is_corresponding":false},{"id":105455,"name":"Sasikanth Manne","orcid":"0000-0001-9856-0871","position":7,"is_corresponding":false},{"id":260596,"name":"Zhendong Cao","orcid":"0000-0002-8189-0169","position":8,"is_corresponding":false},{"id":105448,"name":"Amy E. Baxter","orcid":"0000-0002-1555-0713","position":9,"is_corresponding":false},{"id":567067,"name":"Zhangying Cai","orcid":"0009-0003-7810-3827","position":10,"is_corresponding":false},{"id":260597,"name":"Elizabeth Freilich","orcid":"0009-0009-6866-6398","position":11,"is_corresponding":false},{"id":567917,"name":"Mohammed A. Ali","orcid":null,"position":12,"is_corresponding":false},{"id":105447,"name":"Josephine R. Giles","orcid":"0000-0002-3713-338X","position":13,"is_corresponding":false},{"id":105451,"name":"Jennifer E. Wu","orcid":"0000-0002-9302-8904","position":14,"is_corresponding":false},{"id":105450,"name":"Allison R. Greenplate","orcid":"0000-0002-2614-3072","position":15,"is_corresponding":false},{"id":36445,"name":"Makoto Kurachi","orcid":"0000-0002-7202-7822","position":16,"is_corresponding":false},{"id":105462,"name":"Kito Nzingha","orcid":"0000-0002-8839-5208","position":17,"is_corresponding":false},{"id":567918,"name":"Viktoriya Ekshyyan","orcid":null,"position":18,"is_corresponding":false},{"id":567068,"name":"Zhuoyu Wen","orcid":"0000-0002-0879-6125","position":19,"is_corresponding":false},{"id":178547,"name":"Nancy A. Speck","orcid":"0000-0002-1893-582X","position":20,"is_corresponding":false},{"id":103605,"name":"Alexis Battle","orcid":"0000-0002-5287-627X","position":21,"is_corresponding":false},{"id":227842,"name":"Shelley L. Berger","orcid":"0000-0001-5398-4400","position":22,"is_corresponding":false},{"id":36451,"name":"E. John Wherry","orcid":"0000-0003-0477-1956","position":23,"is_corresponding":false},{"id":260600,"name":"Junwei Shi","orcid":"0000-0002-8427-6316","position":24,"is_corresponding":false},{"id":52789,"name":"Zeyu Chen","orcid":"0000-0001-8534-0829","position":0,"is_corresponding":true}],"reference_count":130,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}