{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:42:22Z","timestamp":1788802942396,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002497"],"award-info":[{"award-number":["82002497"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The six transcriptomic immune subtypes (ISs) (C1 - C6) were reported to have complex and different interplay between TME and cancer cells in TCGA (The Cancer Genome Atlas) pan-cancer cohort. Our study specifically explored how the consequence of interplay determines the prognosis and the response to therapy in LUAD cohorts. Clinical and molecular information of LUAD patients were from TCGA and Gene Expression Omnibus (GEO). The immune cell populations and gene\/pathway enrichment analysis were performed to explore the molecular differences among the C3 IS and other ISs in the LUAD population. The proportion of C3 inflammatory IS was identified as the most common IS in both TCGA (<jats:italic>N =<\/jats:italic> 457) and GEO (<jats:italic>N =<\/jats:italic> 901) cohorts. The C3 IS was also found to be the most accurate prognostic subtype, which was associated with significantly longer OS (p &amp;lt;0.001) and DFS (p &amp;lt;0.001). The C3 IS presented higher levels of CD8 T, M1 macrophage, and myeloid dendritic cells, while lower levels of M2 macrophages and cancer-associated fibroblast cells. Moreover, the C3 subtype was enriched in the antigen process and presenting, interferon-gamma response, T cell receptor signaling, and natural killer cell-mediated cytotoxicity pathways than C1\/C2. In contrast, the C1\/C2 presented greater activation of pathways related to the cell cycles, DNA repair, and p53 signaling pathways. The immune-related C3 IS had a great ability to stratify the prognosis of LUAD, providing clues for further pathogenic research. This classification might help direct precision medicine screenings of LUAD patients, thus possibly improving their prognoses.<\/jats:p>","DOI":"10.3389\/fimmu.2022.877896","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T05:34:40Z","timestamp":1654234480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Immune Subtypes in LUAD Identify Novel Tumor Microenvironment Profiles With Prognostic and Therapeutic Implications"],"prefix":"10.3389","volume":"13","author":[{"given":"Feng","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhentian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.05.021","article-title":"The International Epidemiology of Lung Cancer: Latest Trends, Disparities, and Tumor Characteristics","volume":"11","author":"Cheng","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-Cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139","article-title":"Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome","volume":"313","author":"Galon","year":"2006","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.06.20","article-title":"Lung Adenocarcinoma: From Molecular Basis to Genome-Guided Therapy and Immunotherapy","volume":"9","author":"Chalela","year":"2017","journal-title":"J Thorac Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348","article-title":"Cancer Immunology. 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