REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
PD-L1	Thermo Fisher Scientific	Cat.#17-5983-42
MHC-1	Biolegend	Cat.#311404
MHC-1 blocking	Thermo Fisher Scientific	Cat.#MA1-19027
PD-1 blocking	Selleckchem	Cat.#A2002
STAT1	Cell Signaling Technology	Cat.#9172S
JAK1	Cell Signaling Technology	Cat.#50996
pSTAT1	Cell Signaling Technology	Cat.#9167
IRF1	Cell Signaling Technology	Cat.#8478
β-tubulin	Cell Signaling Technology	Cat.#2146
β-actin	Cell Signaling Technology	Cat.#3700
FLAG	Sigma-Aldrich	Cat.#F3165
CD3	Thermo Fisher Scientific	Cat.#11-0038-42
IFNγ blocking	Thermo Fisher Scientific	Cat.#16-7318-81
CD28	Thermo Fisher Scientific	Cat.#16-0289-81
B2M	Cell Signaling Technology	Cat.#12851
MLH1	Cell Signaling Technology	Cat.#3515
HA	Cell Signaling Technology	Cat.#3724
Bacterial and virus strains
DH5-α E. coli	NEB	Cat.#C2987I
ElectroMAX Stbl4 E. coli	Thermo Fisher Scientific	Cat.#11635018
Biological samples
CRC-9 tumor organoid and autologous PBMC cultures	Cattaneo et al, 201962	N/A
Chemicals, peptides, and recombinant proteins
IFNγ	Thermo Fisher Scientific	Cat.#PHC4031
FuGENE HD	Promega	Cat.#E2311
IL-2	Thermo Fisher Scientific	Cat.#CTP0021
BME	R&D Systems	Cat.#3433-010-R1
Critical commercial assays
IFNγ ELISA	Thermo Fisher Scientific	Cat.#EHIFNG
CellTiter-Glo	Promega	Cat.#G7570
Mission Bio Tapestri single cell sequencing	Mission Bio	N/A
Deposited data
NG BE screens 1 and 2	This paper	ERP131485
NGG IFNG8 BE screens 1 and 2	This paper	ERP130865
amplicon seq. of JAK1	This paper	ERP131486
NGN ABE and CBE screens 1 and 2	This paper	ERP136370
JAK1 BE NGG screen 2	This paper	ERP131487
JAK1 BE NGG screen 1	This paper	ERP136387
CRISPR IO KO screen 2	This paper	ERP136388
CRISPR IO KO screen 1	This paper	ERP136389
CRC-9 NGG IFNG8 BE screens 1 and 2	This paper	ERP137489
MissionBio single cell DNA seq.	This paper	ERP133355
Experimental models: Cell lines
HT-29	NCI	RRID: CVCL_0320
LS-411N	ATCC	RRID: CVCL_1385
OCI-M1	DSMZ	RRID: CVCL_2149
HT55	ECACC	RRID: CVCL_1294
K2	Massachusetts General Hospital, Hensin Tsao	RRID: CVCL_AT85
HEK293T	ATCC	RRID: CVCL_0063
Oligonucleotides
Primers are listed in Table S7	This paper	N/A
Recombinant DNA
BE-FLARE gblock from IDT	IDT and Coelho et al. 201844	N/A
CLYBL-hNGN2-BSD-mApple	Michael Ward lab	Addgene plasmid #124229
YE1-BE4max-Cas9NGN	Doman et al. 202050	Addgene plasmid #138159
Mammalian expression plasmid for transfection	Ran et al. 201385	Addgene plasmid #48140
pKLV2-BFP-Puro lentiviral hU6 gRNA expression vector	Tzelepis et al. 201686	Addgene plasmid #67974
iBE3 CLYBL	This paper	Addgene plasmid #174569
iBE4max YE1 NG CLYBL	This paper	Addgene plasmid #174570
HA-SOCS1	This paper	Addgene plasmid #174571
FLAG-JAK1	This paper	Addgene plasmid #174572
FLAG-JAK1Gly590Arg	This paper	Addgene plasmid #174573
Software and algorithms
Prism 8	GraphPad	N/A
R	Comprehensive R Archive Network R project	N/A
FlowJo	Tree Star	N/A
PyMOL 2.4.1	PyMOL	N/A
Other
www.sanger.ac.uk/tool/be-view	This paper	N/A