{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:25:28Z","timestamp":1785432328519,"version":"3.56.0"},"reference-count":98,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Boehringer Ingelheim"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,20]]},"abstract":"<jats:p>\n                    Cytotoxic CD8 +T lymphocytes (CTLs) are key players of adaptive anti-tumor immunity based on their ability to specifically recognize and destroy tumor cells. Many cancer immunotherapies rely on unleashing CTL function. However, tumors can evade killing through strategies which are not yet fully elucidated. To provide deeper insight into tumor evasion mechanisms in an antigen-dependent manner, we established a human co-culture system composed of tumor and primary immune cells. Using this system, we systematically investigated intrinsic regulators of tumor resistance by conducting a complementary CRISPR screen approach. By harnessing CRISPR activation (CRISPRa) and CRISPR knockout (KO) technology in parallel, we investigated gene gain-of-function as well as loss-of-function across genes with annotated function in a colon carcinoma cell line. CRISPRa and CRISPR KO screens uncovered 187 and 704 hits, respectively, with 60 gene hits overlapping between both. These data confirmed the role of interferon-\u03b3 (IFN-\u03b3), tumor necrosis factor \u03b1 (TNF-\u03b1) and autophagy pathways and uncovered novel genes implicated in tumor resistance to killing. Notably, we discovered that\n                    <jats:italic>ILKAP<\/jats:italic>\n                    encoding the integrin-linked kinase-associated serine\/threonine phosphatase 2 C, a gene previously unknown to play a role in antigen specific CTL-mediated killing, mediate tumor resistance independently from regulating antigen presentation, IFN-\u03b3 or TNF-\u03b1 responsiveness. Moreover, our work describes the contrasting role of soluble and membrane-bound ICAM-1 in regulating tumor cell killing. The deficiency of membrane-bound ICAM-1 (mICAM-1) or the overexpression of soluble ICAM-1 (sICAM-1) induced resistance to CTL killing, whereas PD-L1 overexpression had no impact. These results highlight the essential role of ICAM-1 at the immunological synapse between tumor and CTL and the antagonist function of sICAM-1.\n                  <\/jats:p>","DOI":"10.7554\/elife.84314","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T07:55:07Z","timestamp":1695282907000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.84314","source":"Crossref","is-referenced-by-count":11,"title":["Complementary CRISPR screen highlights the contrasting role of membrane-bound and soluble ICAM-1 in regulating antigen-specific tumor cell killing by cytotoxic T cells"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7882-8284","authenticated-orcid":true,"given":"Ann-Kathrin","family":"Herzfeldt","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6047-8200","authenticated-orcid":true,"given":"Marta Puig","family":"Gamez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Martin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Drug Discovery Sciences, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-1071","authenticated-orcid":true,"given":"Lukasz Miloslaw","family":"Boryn","sequence":"additional","affiliation":[{"name":"Ardigen SA","place":["Krak\u00f3w, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-3516","authenticated-orcid":true,"given":"Praveen","family":"Baskaran","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Global Computational Biology and Digital Sciences, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-2971","authenticated-orcid":true,"given":"Heinrich J","family":"Huber","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Drug Discovery Sciences, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schuler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Drug Discovery Sciences, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-6026","authenticated-orcid":true,"given":"John E","family":"Park","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Kim","family":"Swee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00q32j219","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim","place":["Biberach an der Riss, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11100988","article-title":"RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma","volume":"11","author":"Alaterre","year":"2021","journal-title":"Journal of Personalized Medicine"},{"key":"bib2","article-title":"CBDD: computational biology methods for drug discovery","volume-title":"Clarivate","author":"Analytics","year":"2021","unstructured":"Analytics C. 2021. CBDD: computational biology methods for drug discovery. Clarivate."},{"key":"bib3","doi-asserted-by":"publisher","first-page":"6437","DOI":"10.1073\/pnas.0502467102","article-title":"Distinct role of lymphocyte function-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes","volume":"102","author":"Anikeeva","year":"2005","journal-title":"PNAS"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.cell.2016.01.021","article-title":"Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing","volume":"165","author":"Basu","year":"2016","journal-title":"Cell"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.4049\/jimmunol.147.12.4398","article-title":"Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity","volume":"147","author":"Becker","year":"1991","journal-title":"Journal of Immunology"},{"key":"bib6","doi-asserted-by":"crossref","first-page":"7224","DOI":"10.4049\/jimmunol.151.12.7224","article-title":"Soluble intercellular adhesion molecule-1 inhibits MHC-restricted specific T cell\/tumor interaction","volume":"151","author":"Becker","year":"1993","journal-title":"Journal of Immunology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.ccell.2022.06.001","article-title":"Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence","volume":"40","author":"Belk","year":"2022","journal-title":"Cancer Cell"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1002\/eji.1830240933","article-title":"Distinct binding of T lymphocytes to ICAM-1, -2 or -3 upon activation of LFA-1","volume":"24","author":"Binnerts","year":"1994","journal-title":"European Journal of Immunology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1002\/eji.202048994","article-title":"Mechanism of action of PD-1 receptor\/ligand targeted cancer immunotherapy","volume":"51","author":"Borst","year":"2021","journal-title":"European Journal of Immunology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.scitotenv.2016.06.239","article-title":"Identifying multiple stressor controls on phytoplankton dynamics in the River Thames (UK) using high-frequency water quality data","volume":"569\u2013570","author":"Bowes","year":"2016","journal-title":"The Science of the Total Environment"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/gcc.22468","article-title":"Mutation patterns in genes encoding interferon signaling and antigen presentation: A pan-cancer survey with implications for the use of immune checkpoint inhibitors","volume":"56","author":"Budczies","year":"2017","journal-title":"Genes, Chromosomes & Cancer"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","article-title":"ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis","volume":"108","author":"Bui","year":"2020","journal-title":"Journal of Leukocyte Biology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1083\/jcb.123.4.1007","article-title":"ICAM-3 interacts with LFA-1 and regulates the LFA-1\/ICAM-1 cell adhesion pathway","volume":"123","author":"Campanero","year":"1993","journal-title":"The Journal of Cell Biology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1073\/pnas.96.6.3017","article-title":"Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily","volume":"96","author":"Casasnovas","year":"1999","journal-title":"PNAS"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/nmeth.3312","article-title":"Highly efficient Cas9-mediated transcriptional programming","volume":"12","author":"Chavez","year":"2015","journal-title":"Nature Methods"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1093\/bioinformatics\/btx364","article-title":"UpSetR: an R package for the visualization of intersecting sets and their properties","volume":"33","author":"Conway","year":"2017","journal-title":"Bioinformatics"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.3390\/ph14010031","article-title":"The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors","volume":"14","author":"Das","year":"2020","journal-title":"Pharmaceuticals"},{"key":"bib18","article-title":"Depmap 20Q4 public","volume-title":"Depmap","author":"DepMap","year":"2020","unstructured":"DepMap. 2020. Depmap 20Q4 public. Depmap."},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65324-2","article-title":"Colorectal cancer is associated with increased circulating lipopolysaccharide, inflammation and hypercoagulability","volume":"10","author":"de Waal","year":"2020","journal-title":"Scientific Reports"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nrg.2017.97","article-title":"Am I ready for CRISPR? A user\u2019s guide to genetic screens","volume":"19","author":"Doench","year":"2018","journal-title":"Nature Reviews. Genetics"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00357-7","article-title":"IFN-\u03b3 surmounts PD-L1\/PD1 inhibition to CAR-T cell therapy by upregulating ICAM-1 on tumor cells","volume":"6","author":"Dong","year":"2021","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1158\/1078-0432.CCR-08-1585","article-title":"Role of ADAMs in cancer formation and progression","volume":"15","author":"Duffy","year":"2009","journal-title":"Clinical Cancer Research"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29604-2","article-title":"ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes","volume":"8","author":"Figenschau","year":"2018","journal-title":"Scientific Reports"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1038\/sj.onc.1205684","article-title":"Matrix metalloproteinase 9 (MMP-9\/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity","volume":"21","author":"Fiore","year":"2002","journal-title":"Oncogene"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1158\/0008-5472.CAN-12-2569","article-title":"CD103 or LFA-1 engagement at the immune synapse between cytotoxic T cells and tumor cells promotes maturation and regulates T-cell effector functions","volume":"73","author":"Franciszkiewicz","year":"2013","journal-title":"Cancer Research"},{"key":"bib26","first-page":"4253","article-title":"Stimulation of tumor growth by human soluble intercellular adhesion molecule-1","volume":"61","author":"Gho","year":"2001","journal-title":"Cancer Research"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5768-0","article-title":"A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic\/prognostic potential","volume":"19","author":"Gobin","year":"2019","journal-title":"BMC Cancer"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"111882","DOI":"10.18632\/oncotarget.22948","article-title":"ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR-124 upregulation","volume":"8","author":"Gu","year":"2017","journal-title":"Oncotarget"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"12729","DOI":"10.1073\/pnas.0902621106","article-title":"Cluster size regulates protein sorting in the immunological synapse","volume":"106","author":"Hartman","year":"2009","journal-title":"PNAS"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19760","article-title":"Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation","volume":"5","author":"Horlbeck","year":"2016","journal-title":"eLife"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001819","article-title":"Integrating genome-wide CRISPR immune screen with multi-omic clinical data reveals distinct classes of tumor intrinsic immune regulators","volume":"9","author":"Hou","year":"2021","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/bjc.2017.434","article-title":"Mechanisms of resistance to immune checkpoint inhibitors","volume":"118","author":"Jenkins","year":"2018","journal-title":"British Journal of Cancer"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"3401","DOI":"10.4049\/jimmunol.174.6.3401","article-title":"The role of intercellular adhesion molecule-1\/LFA-1 interactions in the generation of tumor-specific CD8+ T cell responses","volume":"174","author":"Jenkinson","year":"2005","journal-title":"Journal of Immunology"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29205-8","article-title":"CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity","volume":"13","author":"Joung","year":"2022","journal-title":"Nature Communications"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"6830","DOI":"10.1073\/pnas.121186998","article-title":"Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion","volume":"98","author":"Jun","year":"2001","journal-title":"PNAS"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41577-019-0218-4","article-title":"Tumour-intrinsic resistance to immune checkpoint blockade","volume":"20","author":"Kalbasi","year":"2020","journal-title":"Nature Reviews. Immunology"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aar3451","article-title":"Tumor immune evasion arises through loss of TNF sensitivity","volume":"3","author":"Kearney","year":"2018","journal-title":"Science Immunology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"450","DOI":"10.15252\/emmm.201404414","article-title":"A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes","volume":"7","author":"Khandelwal","year":"2015","journal-title":"EMBO Molecular Medicine"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bar030","article-title":"Ensembl BioMarts: a hub for data retrieval across taxonomic space","volume":"2011","author":"Kinsella","year":"2011","journal-title":"Database"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00709-7","article-title":"pH-responsive antibodies for therapeutic applications","volume":"28","author":"Klaus","year":"2021","journal-title":"Journal of Biomedical Science"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41586-020-2746-2","article-title":"Functional genomic landscape of cancer-intrinsic evasion of killing by T cells","volume":"586","author":"Lawson","year":"2020","journal-title":"Nature"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1161\/CIRCULATIONAHA.105.595918","article-title":"Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue","volume":"114","author":"Lee","year":"2006","journal-title":"Circulation"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1093\/emboj\/20.9.2160","article-title":"Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1","volume":"20","author":"Leung-Hagesteijn","year":"2001","journal-title":"The EMBO Journal"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0843-6","article-title":"Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR","volume":"16","author":"Li","year":"2015","journal-title":"Genome Biology"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120803","article-title":"Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression","volume":"128","author":"Lin","year":"2018","journal-title":"The Journal of Clinical Investigation"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92332-7","article-title":"A genome-wide CRISPR\/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells","volume":"11","author":"Lindner","year":"2021","journal-title":"Scientific Reports"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ejca.2016.02.022","article-title":"The integrin-linked kinase-associated phosphatase (ILKAP) is a regulatory hub of ovarian cancer cell susceptibility to platinum drugs","volume":"60","author":"Lorenzato","year":"2016","journal-title":"European Journal of Cancer"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nature23270","article-title":"In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target","volume":"547","author":"Manguso","year":"2017","journal-title":"Nature"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/0092-8674(87)90104-8","article-title":"Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1)","volume":"51","author":"Marlin","year":"1987","journal-title":"Cell"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.Journal"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"3578","DOI":"10.4049\/jimmunol.155.7.3578","article-title":"Characterization of intercellular adhesion molecule-1 ectodomain (sICAM-1) as an inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1","volume":"155","author":"Meyer","year":"1995","journal-title":"The Journal of Immunology"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212053","article-title":"SLFN11 can sensitize tumor cells towards IFN-\u03b3-mediated T cell killing","volume":"14","author":"Mezzadra","year":"2019","journal-title":"PLOS ONE"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41592-020-0850-8","article-title":"Multilayered VBC score predicts sgRNAs that efficiently generate loss-of-function alleles","volume":"17","author":"Michlits","year":"2020","journal-title":"Nature Methods"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1084\/jem.182.5.1231","article-title":"Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1","volume":"182","author":"Miller","year":"1995","journal-title":"The Journal of Experimental Medicine"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020232","article-title":"ADAM10-Mediated cleavage of ICAM-1 is involved in Neutrophil Transendothelial Migration","volume":"10","author":"Morsing","year":"2021","journal-title":"Cells"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/science.aao1710","article-title":"A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing","volume":"359","author":"Pan","year":"2018","journal-title":"Science"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature23477","article-title":"Identification of essential genes for cancer immunotherapy","volume":"548","author":"Patel","year":"2017","journal-title":"Nature"},{"key":"bib58","article-title":"Patchwork: the composer of plots","volume-title":"Patchwork","author":"Pedersen","year":"2020","unstructured":"Pedersen TL. 2020. Patchwork: the composer of plots. Patchwork."},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18570-x","article-title":"PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade","volume":"11","author":"Peng","year":"2020","journal-title":"Nature Communications"},{"key":"bib60","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12242","article-title":"A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion","volume":"7","author":"Petit","year":"2016","journal-title":"Nature Communications"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"4469","DOI":"10.4049\/jimmunol.1400135","article-title":"ICAM-1: isoforms and phenotypes","volume":"192","author":"Ramos","year":"2014","journal-title":"Journal of Immunology"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Research"},{"key":"bib63","article-title":"R: A language and environment for statistical computing","author":"R Development Core Team","year":"2022","unstructured":"R Development Core Team. 2022. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. https:\/\/www.r-project.org\/index.html."},{"key":"bib64","doi-asserted-by":"publisher","first-page":"529","DOI":"10.4049\/jimmunol.155.2.529","article-title":"The native structure of intercellular adhesion molecule-1 (ICAM-1) is a dimer. Correlation with binding to LFA-1","volume":"155","author":"Reilly","year":"1995","journal-title":"Journal of Immunology"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1002\/eji.200323195","article-title":"ICAM-1 isoforms: specific activity and sensitivity to cleavage by leukocyte elastase and cathepsin G","volume":"33","author":"Robledo","year":"2003","journal-title":"European Journal of Immunology"},{"key":"bib67","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4508794","article-title":"Current challenges in cancer immunotherapy: multimodal approaches to improve efficacy and patient response rates","volume":"2019","author":"Sambi","year":"2019","journal-title":"Journal of Oncology"},{"key":"bib68","article-title":"Rrvgo: a Bioconductor package to reduce and visualize gene Ontology terms","volume-title":"Rrvgo","author":"Sayols","year":"2020","unstructured":"Sayols S. 2020. Rrvgo: a Bioconductor package to reduce and visualize gene Ontology terms. Rrvgo."},{"key":"bib69","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/s00384-018-3198-0","article-title":"Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma","volume":"34","author":"Schellerer","year":"2019","journal-title":"International Journal of Colorectal Disease"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj4008","article-title":"CRISPR activation and interference screens decode stimulation responses in primary human T cells","volume":"375","author":"Schmidt","year":"2022","journal-title":"Science"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.ccell.2020.03.017","article-title":"Acquired resistance to immune checkpoint inhibitors","volume":"37","author":"Schoenfeld","year":"2020","journal-title":"Cancer Cell"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.immuni.2007.12.016","article-title":"Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory","volume":"28","author":"Scholer","year":"2008","journal-title":"Immunity"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0140-6736(91)90077-3","article-title":"Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders","volume":"338","author":"Seth","year":"1991","journal-title":"Lancet"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1016\/j.cell.2018.10.024","article-title":"Genome-wide CRISPR Screens in Primary Human T Cells reveal Key regulators of immune function","volume":"175","author":"Shifrut","year":"2018","journal-title":"Cell"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/path.4546","article-title":"Soluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment","volume":"236","author":"Suarez-Carmona","year":"2015","journal-title":"The Journal of Pathology"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Research"},{"key":"bib78","article-title":"KEGGREST: client-side REST access to the Kyoto encyclopedia of genes and Genomes (KEGG)","volume-title":"KEGGREST","author":"Tenenbaum","year":"2020","unstructured":"Tenenbaum D. 2020. KEGGREST: client-side REST access to the Kyoto encyclopedia of genes and Genomes (KEGG). KEGGREST."},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00196-x","article-title":"Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy","volume":"5","author":"Thelen","year":"2021","journal-title":"NPJ Precision Oncology"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-4757-3294-8","volume-title":"Modeling Survival Data: Extending the Cox Model","author":"Therneau","year":"2000"},{"key":"bib81","article-title":"A package for survival analysis in R","volume-title":"R Project","author":"Therneau","year":"2022","unstructured":"Therneau TM. 2022. A package for survival analysis in R. R Project."},{"key":"bib82","doi-asserted-by":"publisher","first-page":"C55","DOI":"10.1152\/ajpcell.00585.2003","article-title":"Signals mediating cleavage of intercellular adhesion molecule-1","volume":"287","author":"Tsakadze","year":"2004","journal-title":"American Journal of Physiology-Cell Physiology"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"3157","DOI":"10.1074\/jbc.M510797200","article-title":"Tumor necrosis factor-alpha-converting enzyme (TACE\/ADAM-17) mediates the ectodomain cleavage of intercellular adhesion molecule-1 (ICAM-1)","volume":"281","author":"Tsakadze","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","article-title":"Defining a cancer dependency map","volume":"170","author":"Tsherniak","year":"2017","journal-title":"Cell"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.cell.2012.09.044","article-title":"STATs shape the active enhancer landscape of T cell populations","volume":"151","author":"Vahedi","year":"2012","journal-title":"Cell"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/nrd4390","article-title":"Is there new hope for therapeutic matrix metalloproteinase inhibition?","volume":"13","author":"Vandenbroucke","year":"2014","journal-title":"Nature Reviews. Drug Discovery"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.cell.2019.06.014","article-title":"Augmenting immunotherapy impact by lowering Tumor TNF Cytotoxicity Threshold","volume":"178","author":"Vredevoogd","year":"2019","journal-title":"Cell"},{"key":"bib88","doi-asserted-by":"publisher","DOI":"10.1016\/j.iotech.2021.100043","article-title":"The (re)discovery of tumor-intrinsic determinants of immune sensitivity by functional genetic screens","volume":"11","author":"Vredevoogd","year":"2021","journal-title":"Immuno-Oncology Technology"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3109\/15419069509081014","article-title":"A distinct mRNA encoding a soluble form of ICAM-1 molecule expressed in Human Tissues","volume":"3","author":"Wakatsuki","year":"1995","journal-title":"Cell Adhesion and Communication"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1093\/bioinformatics\/btm087","article-title":"A new method to measure the semantic similarity of GO terms","volume":"23","author":"Wang","year":"2007","journal-title":"Bioinformatics"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41596-018-0113-7","article-title":"Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute","volume":"14","author":"Wang","year":"2019","journal-title":"Nature Protocols"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix Metalloproteinase inhibitors in Cancer Therapy: turning past failures into future successes","volume":"17","author":"Winer","year":"2018","journal-title":"Molecular Cancer Therapeutics"},{"key":"bib93","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153029","article-title":"Soluble intercellular cell adhesion molecule-1 in lung cancer: A meta-analysis","volume":"216","author":"Wu","year":"2020","journal-title":"Pathology, Research and Practice"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/s1097-2765(04)00204-7","article-title":"Structural basis for dimerization of ICAM-1 on the cell surface","volume":"14","author":"Yang","year":"2004","journal-title":"Molecular Cell"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1172\/JCI83871","article-title":"Cancer immunotherapy: harnessing the immune system to battle cancer","volume":"125","author":"Yang","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.cmet.2022.02.009","article-title":"A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as A means to enhance CAR-T therapy","volume":"34","author":"Ye","year":"2022","journal-title":"Cell Metabolism"},{"key":"bib97","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb9561","article-title":"Autophagy protects tumors from T cell-mediated cytotoxicity via inhibition of TNF\u03b1-induced apoptosis","volume":"5","author":"Young","year":"2020","journal-title":"Science Immunology"},{"key":"bib98","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-244","article-title":"RCircos: an R package for Circos 2D track plots","volume":"14","author":"Zhang","year":"2013","journal-title":"BMC Bioinformatics"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/84314\/elife-84314-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/84314\/elife-84314-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/84314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T06:45:52Z","timestamp":1697697952000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/84314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":98,"alternative-id":["10.7554\/eLife.84314"],"URL":"https:\/\/doi.org\/10.7554\/elife.84314","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.08.26.505456","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.08.26.505456","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.08.26.505456","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.84314.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.84314.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.84314.sa0","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e84314"}}