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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Long non-coding RNAs (lncRNAs) are critical regulators of the tumor microenvironment (TME); however, their cell-specific roles in predicting immunotherapy response in breast cancer (BC) remain poorly understood. This study aimed to identify immune cell-specific lncRNA signatures associated with potential pembrolizumab responsiveness by analyzing single-cell RNA sequencing data from 27 BC patients, including luminal and triple-negative (TNBC) subtypes. Differential expression analysis was performed across myeloid, lymphocyte, and dendritic cells, comparing groups based on lymphocyte expansion as a potential responsiveness criterion, classified as lymphocyte clonal expansion (E) and those without or with limited clonal expansion (NE, non-expansion). In luminal patients, potential responsiveness was primarily linked to macrophage-driven lncRNA activity. MUC20-OT1 was upregulated in responders, while LINC01094, a transcript associated with pro-tumoral M2 polarization and immune escape, was elevated in macrophages from non-responders. Conversely, TNBC responders exhibited a lymphocyte-dominant signature, characterized by the upregulation of LINC01871, LINC01943, and MIR4435-2HG. Notably, NEAT1 was uniquely identified as a significantly upregulated marker in dendritic cells of TNBC responders. While NEAT1 is known to modulate T cell abundance and thwart immune evasion in other contexts, its role in BC-associated dendritic cells remains a novel and promising area for investigation. Collectively, these findings demonstrate that lncRNA signatures in the TME are pivotal for understanding pembrolizumab sensitivity. The shift from macrophage-centered lncRNA activity in luminal subtypes to a lymphocyte- and dendritic cell-dominant profile in TNBC underscores the necessity of subtype-specific approaches. These identified lncRNAs emerge as promising candidate biomarkers associated with T cell expansion and potential response to pembrolizumab treatment to refine patient stratification and improve immunotherapeutic outcomes.<\/jats:p>","DOI":"10.3390\/ijms27198606","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering Immune Cell\u2013Specific lncRNAs as Anti-PD-1 Response-Associated Markers in Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Clayton","family":"Voidelo","sequence":"first","affiliation":[{"name":"Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paran\u00e1, Curitiba 81530-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Thalita Maria","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Department of Informatics, Federal University of Paran\u00e1, Curitiba 81530-980, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7925-7698","authenticated-orcid":false,"given":"Regiane Stafim","family":"da Cunha","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paran\u00e1, Curitiba 81530-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jaqueline Carvalho","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paran\u00e1, Curitiba 81530-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3163-8600","authenticated-orcid":false,"given":"Carolina","family":"Mathias","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paran\u00e1, Curitiba 81530-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long Non-Coding RNAs: Definitions, Functions, Challenges and Recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat. 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