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oai:figshare.com:article/33949840 2026-09-21T05:34:31Z category_12 portal_316 item_type_3 month_year_09_2026

Table 1_Integrated single-cell and multi-cohort analyses reveal CTCF as a key regulator of chemo-immunotherapy resistance in lung adenocarcinoma.docx Hui Chen (28597) Taiyang Zhang (1587388) Yiwei Zhang (1448599) Mohan Li (7527596) Haoran Yang (1551835) Yue Zhang (30585) Feng Xu (89016) Cell Biology CD276 chemo-immunotherapy resistance CTCF immune microenvironment non-small cell lung cancer tumor cell state Background<p>Chemo-immunotherapy has improved clinical outcomes in non-small cell lung cancer (NSCLC), but resistance remains a major challenge. The tumor cell states and molecular mechanisms underlying treatment resistance are not fully understood.</p>Methods<p>Single-cell RNA sequencing data from NSCLC patients receiving chemo-immunotherapy were integrated with public transcriptomic cohorts and functional experiments. Resistance-associated tumor cell populations were identified, and key regulatory factors were investigated through bioinformatic analyses and experimental validation.</p>Results<p>Single-cell analysis identified a malignant epithelial cell subpopulation enriched in patients with stable disease, suggesting a resistance-associated tumor cell state. Genes derived from this population were associated with unfavorable prognosis and were used to construct a prognostic model with consistent performance across multiple independent cohorts. Among the candidate genes, CTCF was identified as a key regulator associated with poor survival and reduced immune infiltration. In an orthotopic lung tumor model, Ctcf knockdown enhanced the antitumor efficacy of pemetrexed combined with anti-PD-1 treatment and promoted CD8⁺ T-cell activity. Mechanistically, CTCF directly upregulated RRM2 and CD276, which mediated chemotherapy resistance and immune suppression, respectively.</p>Conclusion<p>Our findings identify CTCF as a critical regulator of chemo-immunotherapy resistance in NSCLC. The CTCF–RRM2/CD276 axis links tumor-intrinsic drug resistance with immune evasion and may represent a potential therapeutic target.</p> 2026-09-21T05:34:31Z Dataset Dataset 10.3389/fcell.2026.1922944.s005 https://figshare.com/articles/dataset/Table_1_Integrated_single-cell_and_multi-cohort_analyses_reveal_CTCF_as_a_key_regulator_of_chemo-immunotherapy_resistance_in_lung_adenocarcinoma_docx/33949840 CC BY 4.0