{
"@context": "/terms/",
"@id": "/publications/6cc80a53-4ca1-4bd4-9942-f0f335b7ec20/",
"@type": [
"Publication",
"Item"
],
"abstract": "Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapies. Here we developed pooled, epigenetic CRISPR screening approaches to systematically profile the effects of activating or repressing 120 transcriptional and epigenetic regulators on human CD8+ T cell state. We found that BATF3 overexpression promoted specific features of memory T cells and attenuated gene programs associated with cytotoxicity, regulatory T cell function, and exhaustion. Upon chronic antigen stimulation, BATF3 overexpression countered phenotypic and epigenetic signatures of T cell exhaustion. Moreover, BATF3 enhanced the potency of CAR T cells in both in vitro and in vivo tumor models and programmed a transcriptional profile that correlates with positive clinical response to adoptive T cell therapy. Finally, we performed CRISPR knockout screens that defined cofactors and downstream mediators of the BATF3 gene network.",
"aliases": [
"charles-gersbach:cd8pos-crispr-screens-nat-genetics-mccutcheon-et-al-2023"
],
"audit": {},
"authors": "Sean R McCutcheon, Adam M Swartz, Michael C Brown, Alejandro Barrera, Christian McRoberts Amador, Keith Siklenka, Lucas Humayun, Maria A Ter Weele, James M Isaacs, Timothy E Reddy, Andrew S Allen, Smita K Nair, Scott J Antonia, Charles A Gersbach",
"award": {
"@id": "/awards/HG012053/",
"component": "functional characterization"
},
"creation_timestamp": "2024-08-07T19:09:43.051420+00:00",
"donors": [],
"file_sets": [
"/analysis-sets/IGVFDS7239LNZO/",
"/measurement-sets/IGVFDS5281AOTI/",
"/measurement-sets/IGVFDS2750APKO/",
"/measurement-sets/IGVFDS4368CMNC/",
"/measurement-sets/IGVFDS4325LQED/",
"/measurement-sets/IGVFDS6373KKOW/",
"/measurement-sets/IGVFDS7967GRIT/",
"/measurement-sets/IGVFDS5292QYYE/",
"/measurement-sets/IGVFDS5328ZNKL/",
"/measurement-sets/IGVFDS0965VVJT/",
"/measurement-sets/IGVFDS3198NMHN/",
"/measurement-sets/IGVFDS4663XDBF/",
"/measurement-sets/IGVFDS8981FZRC/",
"/measurement-sets/IGVFDS7501PRYR/",
"/measurement-sets/IGVFDS9111EVGC/",
"/measurement-sets/IGVFDS9825YLAW/",
"/measurement-sets/IGVFDS6764PIJI/",
"/measurement-sets/IGVFDS1675WFHV/",
"/measurement-sets/IGVFDS0238VKNF/",
"/measurement-sets/IGVFDS3644PCDG/",
"/measurement-sets/IGVFDS6164ZDND/",
"/measurement-sets/IGVFDS1219SFUJ/",
"/measurement-sets/IGVFDS2160ZTSJ/",
"/measurement-sets/IGVFDS4954WWBW/",
"/measurement-sets/IGVFDS0707NWZU/",
"/measurement-sets/IGVFDS7935RKIM/",
"/measurement-sets/IGVFDS5042DREX/",
"/measurement-sets/IGVFDS6156TPWX/",
"/measurement-sets/IGVFDS3539CPFW/",
"/measurement-sets/IGVFDS4959TRIO/",
"/measurement-sets/IGVFDS6791MFOC/",
"/measurement-sets/IGVFDS9846EQXV/",
"/measurement-sets/IGVFDS4636NLRL/",
"/measurement-sets/IGVFDS5627DEFZ/",
"/measurement-sets/IGVFDS9576VGSP/",
"/measurement-sets/IGVFDS7661MIEF/",
"/measurement-sets/IGVFDS4213FGQT/",
"/measurement-sets/IGVFDS7534QWMG/",
"/measurement-sets/IGVFDS4930BLTW/",
"/measurement-sets/IGVFDS5130AKAZ/",
"/measurement-sets/IGVFDS0140NIXT/",
"/measurement-sets/IGVFDS6262JHMS/",
"/measurement-sets/IGVFDS4149GPKB/",
"/measurement-sets/IGVFDS2737CQNK/",
"/measurement-sets/IGVFDS4169BMPH/",
"/measurement-sets/IGVFDS0870PAHS/",
"/measurement-sets/IGVFDS0416TFEL/",
"/measurement-sets/IGVFDS3969UCCQ/",
"/measurement-sets/IGVFDS5357XHOF/",
"/measurement-sets/IGVFDS3559YNWI/",
"/measurement-sets/IGVFDS3910ZTSZ/",
"/measurement-sets/IGVFDS5417LSWU/",
"/measurement-sets/IGVFDS5910YZFG/",
"/measurement-sets/IGVFDS5416ROJO/",
"/measurement-sets/IGVFDS5049UPEO/",
"/measurement-sets/IGVFDS1619VKNB/",
"/measurement-sets/IGVFDS4808GJDM/",
"/measurement-sets/IGVFDS1336JNHX/",
"/measurement-sets/IGVFDS3760HQCL/",
"/measurement-sets/IGVFDS5951POJU/",
"/measurement-sets/IGVFDS6902RBPO/",
"/measurement-sets/IGVFDS8967NSST/",
"/measurement-sets/IGVFDS7858OVUD/",
"/measurement-sets/IGVFDS0986HRDF/",
"/measurement-sets/IGVFDS6590HDLA/",
"/measurement-sets/IGVFDS1333MBPK/",
"/measurement-sets/IGVFDS6088VPGO/",
"/measurement-sets/IGVFDS4586UCAI/",
"/measurement-sets/IGVFDS3810SJRN/",
"/measurement-sets/IGVFDS4221ZTFC/",
"/measurement-sets/IGVFDS9813VHFD/",
"/measurement-sets/IGVFDS9674AATW/",
"/auxiliary-sets/IGVFDS9108NLTS/",
"/auxiliary-sets/IGVFDS8372HZNT/",
"/auxiliary-sets/IGVFDS1345STXL/",
"/auxiliary-sets/IGVFDS0128XYUT/",
"/auxiliary-sets/IGVFDS1381JNPK/",
"/auxiliary-sets/IGVFDS0993OMZM/",
"/auxiliary-sets/IGVFDS7413JPIS/",
"/auxiliary-sets/IGVFDS8876GCAP/",
"/auxiliary-sets/IGVFDS5825GTXD/",
"/auxiliary-sets/IGVFDS3348HSLB/",
"/auxiliary-sets/IGVFDS4170XDRQ/",
"/auxiliary-sets/IGVFDS6878SUMX/",
"/auxiliary-sets/IGVFDS9073AJJA/",
"/auxiliary-sets/IGVFDS1323NNMG/",
"/auxiliary-sets/IGVFDS6052SPEY/",
"/auxiliary-sets/IGVFDS3945FAEL/",
"/auxiliary-sets/IGVFDS8029DSPH/",
"/auxiliary-sets/IGVFDS5759ZVUX/",
"/auxiliary-sets/IGVFDS2210LUUT/",
"/auxiliary-sets/IGVFDS9310VIMF/",
"/auxiliary-sets/IGVFDS8113ANRK/",
"/auxiliary-sets/IGVFDS5741RXXI/",
"/auxiliary-sets/IGVFDS2399UCGA/",
"/auxiliary-sets/IGVFDS0506WOIW/",
"/auxiliary-sets/IGVFDS9580JWWG/",
"/auxiliary-sets/IGVFDS6947GSPF/",
"/auxiliary-sets/IGVFDS3944URNH/",
"/auxiliary-sets/IGVFDS0591VNKJ/",
"/auxiliary-sets/IGVFDS2625BWKZ/",
"/auxiliary-sets/IGVFDS2606RJRX/",
"/auxiliary-sets/IGVFDS1046ZFUG/",
"/auxiliary-sets/IGVFDS4215TFWE/",
"/auxiliary-sets/IGVFDS3707AOAO/",
"/auxiliary-sets/IGVFDS7828ZYHS/",
"/auxiliary-sets/IGVFDS8866USWP/",
"/auxiliary-sets/IGVFDS9693EKGR/",
"/auxiliary-sets/IGVFDS3536DHAB/",
"/auxiliary-sets/IGVFDS6547DKWF/",
"/auxiliary-sets/IGVFDS3370BGRA/",
"/auxiliary-sets/IGVFDS8972XOSG/",
"/auxiliary-sets/IGVFDS0334XGBU/",
"/auxiliary-sets/IGVFDS5903JKGX/",
"/auxiliary-sets/IGVFDS7251RDFD/",
"/auxiliary-sets/IGVFDS2036IYZB/",
"/auxiliary-sets/IGVFDS8935CYSH/",
"/auxiliary-sets/IGVFDS3792YMVB/",
"/analysis-sets/IGVFDS5157TBYH/",
"/analysis-sets/IGVFDS8839AFQB/",
"/analysis-sets/IGVFDS9143TFRW/",
"/analysis-sets/IGVFDS5106XTZH/",
"/analysis-sets/IGVFDS8364HJHL/",
"/analysis-sets/IGVFDS0320JXJG/",
"/analysis-sets/IGVFDS2261TIMI/",
"/analysis-sets/IGVFDS7196OWBU/",
"/analysis-sets/IGVFDS4582MPNU/",
"/analysis-sets/IGVFDS3319RFFN/",
"/analysis-sets/IGVFDS2302NLIO/",
"/analysis-sets/IGVFDS4011VZXE/",
"/analysis-sets/IGVFDS9906UGWB/",
"/analysis-sets/IGVFDS6344XBAV/",
"/analysis-sets/IGVFDS5498STRV/",
"/analysis-sets/IGVFDS2716FVEL/",
"/analysis-sets/IGVFDS9065THHI/",
"/analysis-sets/IGVFDS5551EATG/",
"/analysis-sets/IGVFDS7944XZYE/",
"/analysis-sets/IGVFDS4488GLKL/",
"/analysis-sets/IGVFDS5478QWPN/",
"/analysis-sets/IGVFDS5218AVPW/",
"/analysis-sets/IGVFDS5066GYDY/",
"/analysis-sets/IGVFDS4430NOFL/",
"/analysis-sets/IGVFDS0006MFFD/",
"/analysis-sets/IGVFDS1013MILB/",
"/analysis-sets/IGVFDS9202ZPBI/",
"/analysis-sets/IGVFDS9445RJOU/",
"/analysis-sets/IGVFDS5239SBBT/",
"/analysis-sets/IGVFDS7714RCSY/",
"/analysis-sets/IGVFDS3105CGSW/",
"/analysis-sets/IGVFDS6924DJJC/",
"/analysis-sets/IGVFDS3609QWUZ/"
],
"journal": "Nature Genetics",
"lab": {
"@id": "/labs/charles-gersbach/",
"title": "Charles Gersbach, Duke"
},
"publication_identifiers": [
"PMID:37945901",
"doi:10.1038/s41588-023-01554-0",
"PMCID:PMC10703699"
],
"published_by": [
"IGVF"
],
"release_timestamp": "2024-10-18T20:04:38.100389+00:00",
"samples": [
"/in-vitro-systems/IGVFSM3606VJWU/",
"/in-vitro-systems/IGVFSM6178KGGZ/",
"/in-vitro-systems/IGVFSM4401YRWQ/",
"/in-vitro-systems/IGVFSM2429HKWG/",
"/in-vitro-systems/IGVFSM3148FRBY/",
"/in-vitro-systems/IGVFSM1838CFFU/",
"/in-vitro-systems/IGVFSM7748IVLZ/",
"/in-vitro-systems/IGVFSM1480DJBL/",
"/in-vitro-systems/IGVFSM8744PJOL/",
"/in-vitro-systems/IGVFSM6964ODEE/",
"/in-vitro-systems/IGVFSM6373RONE/",
"/in-vitro-systems/IGVFSM2737ATVK/",
"/in-vitro-systems/IGVFSM4817IZZH/",
"/in-vitro-systems/IGVFSM3244YHOI/",
"/in-vitro-systems/IGVFSM6490XCFZ/",
"/in-vitro-systems/IGVFSM6721RTTV/",
"/in-vitro-systems/IGVFSM6606RDWT/",
"/in-vitro-systems/IGVFSM5112IFQB/",
"/primary-cells/IGVFSM6537MPGY/",
"/primary-cells/IGVFSM0383IKGE/",
"/primary-cells/IGVFSM9627TJZO/",
"/primary-cells/IGVFSM7117ATUZ/",
"/primary-cells/IGVFSM8879NUYQ/",
"/primary-cells/IGVFSM0619UUOC/",
"/primary-cells/IGVFSM0846TBSG/",
"/primary-cells/IGVFSM6223YCQV/",
"/primary-cells/IGVFSM6508DFUL/",
"/primary-cells/IGVFSM3002NRDK/",
"/primary-cells/IGVFSM2690MTOA/",
"/primary-cells/IGVFSM4694MBIW/",
"/primary-cells/IGVFSM1190UUKW/",
"/primary-cells/IGVFSM7658WDNM/",
"/primary-cells/IGVFSM7030KVXG/",
"/primary-cells/IGVFSM7452ZWAU/",
"/primary-cells/IGVFSM1343OUDU/",
"/primary-cells/IGVFSM1108NFPI/",
"/primary-cells/IGVFSM1498WFCO/",
"/primary-cells/IGVFSM5237UBBW/",
"/primary-cells/IGVFSM2385KZGA/",
"/primary-cells/IGVFSM9946HIBN/",
"/primary-cells/IGVFSM2391CIZT/",
"/primary-cells/IGVFSM2747RJFY/",
"/primary-cells/IGVFSM8800PZZL/",
"/primary-cells/IGVFSM7232YAVV/",
"/primary-cells/IGVFSM6350DJQS/",
"/primary-cells/IGVFSM3073WHFV/",
"/primary-cells/IGVFSM5707IHVB/",
"/primary-cells/IGVFSM2082DWDD/",
"/primary-cells/IGVFSM6002TGBI/",
"/primary-cells/IGVFSM8084QKPW/",
"/primary-cells/IGVFSM5949AWIH/",
"/primary-cells/IGVFSM0829UPAR/",
"/primary-cells/IGVFSM7373RCYG/",
"/primary-cells/IGVFSM8172ZPYG/",
"/primary-cells/IGVFSM2624PYEY/",
"/primary-cells/IGVFSM5189UBOI/",
"/primary-cells/IGVFSM3998OQDA/",
"/primary-cells/IGVFSM9974ALBF/",
"/primary-cells/IGVFSM2824DRGN/",
"/primary-cells/IGVFSM4936HKEW/",
"/primary-cells/IGVFSM1311HWOF/",
"/primary-cells/IGVFSM5367RVVU/",
"/primary-cells/IGVFSM4633QTQY/",
"/primary-cells/IGVFSM8821YQXI/",
"/primary-cells/IGVFSM1730FNFX/",
"/primary-cells/IGVFSM0015KLZS/",
"/primary-cells/IGVFSM5048YTHB/",
"/primary-cells/IGVFSM2624KTRK/",
"/primary-cells/IGVFSM2207SJEN/",
"/primary-cells/IGVFSM3795JDHP/",
"/primary-cells/IGVFSM0066TACG/",
"/primary-cells/IGVFSM4716FORO/",
"/primary-cells/IGVFSM3427LEEW/",
"/primary-cells/IGVFSM7890DZST/",
"/primary-cells/IGVFSM7413JCSK/",
"/primary-cells/IGVFSM7158ADKU/",
"/primary-cells/IGVFSM7887TFLH/",
"/primary-cells/IGVFSM8964QQSX/",
"/primary-cells/IGVFSM7634EVUP/",
"/primary-cells/IGVFSM8036VPRU/",
"/primary-cells/IGVFSM6851CRLW/",
"/primary-cells/IGVFSM3805WZUU/",
"/primary-cells/IGVFSM0218YCAH/",
"/primary-cells/IGVFSM6062UNTJ/",
"/primary-cells/IGVFSM4508IIAY/",
"/primary-cells/IGVFSM9398LTWW/",
"/primary-cells/IGVFSM3895SURE/",
"/primary-cells/IGVFSM7226CVDS/",
"/primary-cells/IGVFSM2105CLXS/",
"/primary-cells/IGVFSM0293OVAT/",
"/primary-cells/IGVFSM8970UORP/",
"/primary-cells/IGVFSM3910UHIY/",
"/primary-cells/IGVFSM7418TTPB/",
"/primary-cells/IGVFSM4110AXZO/",
"/primary-cells/IGVFSM1205VMNO/",
"/primary-cells/IGVFSM0466RHGQ/",
"/primary-cells/IGVFSM1721KPGX/"
],
"schema_version": "6",
"software": [],
"software_versions": [],
"status": "released",
"submitted_by": {
"@id": "/users/29f5f78d-ac90-421e-90c6-a90e1dc407a7/",
"title": "Alejandro Barrera"
},
"summary": "Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens",
"title": "Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens",
"uuid": "6cc80a53-4ca1-4bd4-9942-f0f335b7ec20",
"workflows": []
}