Uncovering Immune Cell-Specific lncRNAs as Anti-PD-1 Response-Associated Markers in Breast Cancer.
- 1Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paraná, Curitiba 81530-000, Brazil.
- 2Department of Informatics, Federal University of Paraná, Curitiba 81530-980, Brazil.
Abstract
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.
Related
- CAMOR and specific oncogene-driven lncRNAs mediate carcinogenic functions downstream of MYC, mutant KRAS, and mutant TP53
- Uncovering KRAS-mutant allele-specific biology and vulnerabilities in non-small cell lung cancer
- Uncovering LINC02982: a T-ALL-specific lncrna linking epigenetic regulation and metabolic pathways
- Speech markers of depression: cross-sectional discrimination, longitudinal association, and treatment response prediction
- Comparing the upregulations of helper T cell-specific activation-induced cell markers (AIM) among COVID-19 vaccinees in Bangladesh
BibTeX
@article{voidelo2026uncovering,
title = {{Uncovering Immune Cell-Specific lncRNAs as Anti-PD-1 Response-Associated Markers in Breast Cancer.}},
author = {Clayton Voidelo and Thalita Maria do Nascimento and Regiane Stafim da Cunha and Jaqueline Carvalho de Oliveira and Carolina Mathias},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198606},
url = {https://europepmc.org/article/MED/42883853},
note = {CC BY},
}
RIS
TY - JOUR
TI - Uncovering Immune Cell-Specific lncRNAs as Anti-PD-1 Response-Associated Markers in Breast Cancer.
AU - Clayton Voidelo
AU - Thalita Maria do Nascimento
AU - Regiane Stafim da Cunha
AU - Jaqueline Carvalho de Oliveira
AU - Carolina Mathias
PY - 2026
DA - 2026/09/26
JO - International journal of molecular sciences
DO - 10.3390/ijms27198606
UR - https://europepmc.org/article/MED/42883853
AB - 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.
SN - 1422-0067
ER -