{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:23:52Z","timestamp":1790400232763,"version":"4.1.0"},"reference-count":35,"publisher":"American Society for Clinical Investigation","issue":"4","funder":[{"name":"NIH","award":["R00AG040149"],"award-info":[{"award-number":["R00AG040149"]}]},{"name":"NSF","award":["1653866"],"award-info":[{"award-number":["1653866"]}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["F1785"],"award-info":[{"award-number":["F1785"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["1147222"],"award-info":[{"award-number":["1147222"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China grants","doi-asserted-by":"crossref","award":["11672246"],"award-info":[{"award-number":["11672246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,21]]},"abstract":"<jats:p>\n                    Immunotherapy has emerged as a promising approach to treat cancer. However, partial responses across multiple clinical trials support the significance of characterizing intertumor and intratumor heterogeneity to achieve better clinical results and as potential tools in selecting patients for different types of cancer immunotherapies. Yet, the type of heterogeneity that informs clinical outcome and patient selection has not been fully explored. In particular, the lack of characterization of immune response\u2013related genes in cancer cells hinders the further development of metrics to select and optimize immunotherapy. Therefore, we analyzed single-cell RNA-Seq data from lung adenocarcinoma patients and cell lines to characterize the intratumor heterogeneity of immune response\u2013related genes and demonstrated their potential impact on the efficacy of immunotherapy. We discovered that IFN-\u03b3 signaling pathway genes are heterogeneously expressed and coregulated with other genes in single cancer cells, including MHC class II (\n                    <jats:italic>MHCII<\/jats:italic>\n                    ) genes. The downregulation of genes in IFN-\u03b3 signaling pathways in cell lines corresponds to an acquired resistance phenotype. Moreover, analysis of 2 groups of tumor-restricted antigens, namely neoantigens and cancer testis antigens, revealed heterogeneity in their expression in single cells. These analyses provide a rationale for applying multiantigen combinatorial therapies to prevent tumor escape and establish a basis for future development of prognostic metrics based on intratumor heterogeneity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.121387","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T11:01:38Z","timestamp":1550660498000},"source":"Crossref","is-referenced-by-count":67,"title":["Single-cell RNA sequencing of lung adenocarcinoma reveals heterogeneity of immune response\u2013related genes"],"prefix":"10.1172","volume":"4","author":[{"given":"Ke-Yue","family":"Ma","sequence":"first","affiliation":[{"name":"Institute for Cellular and Molecular Biology, College of Natural Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra A.","family":"Schonnesen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cockrell School of Engineering, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Brock","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology, College of Natural Sciences,"},{"name":"Department of Biomedical Engineering, Cockrell School of Engineering, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Van Den Berg","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology, College of Natural Sciences,"},{"name":"Department of Oncology, LIVESTRONG Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA."},{"name":"Division of Pharmacology\/Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Gail","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"Department of Oncology, LIVESTRONG Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of AnoRectal Surgery and"},{"name":"Department of Center Laboratory, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-5922","authenticated-orcid":true,"given":"Ning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology, College of Natural Sciences,"},{"name":"Department of Biomedical Engineering, Cockrell School of Engineering, and"},{"name":"Department of Oncology, LIVESTRONG Cancer Institutes, Dell Medical School, The University of Texas at 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