Single-cell sequencing reveals immune landscape of tumor-infiltrating lymphocytes (TILs) during non-small cell lung cancer (NSCLC) progression

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Abstract During the process of NSCLC using TILs therapy, heterogeneity immune cell was revealed by combined single-cell RNA (scRNA)/ T receptor (scTCR) sequencing -seq data from lung adenocarcinoma (LUAD) patients. Naïve CD4 + increased in tumor tissue compared with circulating blood samples, activated signaling pathways were recognized, and GZMA identified as a potential novel diagnostic biomarker. The scTCR-seq repertoire also investigated. At transition state, macrophages ( FTL ) dendritic AIF1 cells transferred most CD3 TCR clones to IL7R cells, cytotoxicity NKG7 transported terminal exhausted CCL5 CD8 cells. expansion helper CXCL13 regulatory FOXP3 expression profiling cytokines, checkpoint receptors their ligands during progression FTL, TNFRSF4 TIGIT CTLA4, show up at initial stage normal metastatic while FGFBP2 , NKG7, PRF1 still appears final samples. Taken together, our study provides single level offers treatment strategies overcome drug resistance.

Language: Английский

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Synergistic B and T lymphocyte interaction: prognostic implications in non-small cell lung cancer

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(3), P. 1227 - 1242

Published: Jan. 1, 2024

While T-cell-mediated immune responses in solid tumors have been well-established and driven major therapeutic advances, our understanding of B-cell biology cancer is comparatively less developed. A total 60 lung patients were included, which 53% diagnosed at an early stage while 47% advanced stage. Flow cytometry was used to analyze the proportion T B cells all blood samples, levels human serum cytokines also assessed. Compared control group, showed lower frequencies IgD+CD27+ marginal CD32+ cells, higher with CD8+ central memory naïve CD4+ cells. Additionally, advanced-stage exhibited cytokines, a effector frequency CD27+CD28+CD4+/CD8+ Linear regression analysis revealed significant correlations between cell subsets, leukocyte count, cytokine levels. Survival demonstrated that class-switched had worse prognosis, CD4+57+ appeared better survival rate. These findings provide valuable insight into immunological changes occur during progression potential inform development new immunotherapeutic strategies.

Language: Английский

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Integrated whole‐exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground‐glass nodules

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(11)

Published: June 1, 2024

Abstract Objective The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from situ (AIS) to minimally invasive (MIA) subsequent (IAC) remains unclear requires further elucidation. We aimed characterize gene mutations expression landscapes, explore association between differentially expressed genes (DEGs) significantly mutated (SMGs) during dynamic evolution AIS IAC. Methods Thirty‐five patients with ground‐glass nodules (GGNs) adenocarcinomas were enrolled. Whole‐exome sequencing (WES) transcriptome (RNA‐Seq) conducted on all patients, encompassing both tumor samples corresponding noncancerous tissues. Data obtained WES RNA‐Seq subsequently analyzed. Results findings delineated that predominant observed EGFR (49%) ANKRD36C (17%). SMGs, including RBM10, associated Meanwhile, DEGs, GPR143, CCR9, ADAMTS16, others entire process LUAD. found signaling pathways related cell migration invasion upregulated, angiogenesis downregulated across pathological stages. Furthermore, we messenger RNA (mRNA) levels FAM83A, MAL2, DEPTOR, correlated CNVs. Gene set enrichment analysis (GSEA) showed heme metabolism cholesterol homeostasis upregulated EGFR/RBM10 co‐mutations, these may have poorer overall survival than those mutations. Based six calculation methods for immune infiltration score, NK/CD8 + T cells decreased, Treg/B increased early Conclusions Our offer valuable insights into unique features LUAD, facilitating identification advancement precision medicine strategies targeting LUAD

Language: Английский

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Leveraging Evolutionary Immunology in Interleukin-6 and Interleukin-17 Signaling for Lung Cancer Therapeutics

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3658 - 3670

Published: Nov. 22, 2024

Lung cancer is among the most common instances of subtypes and associated with high mortality rates. Due to availability fewer therapies delayed clinical investigations, number incidences rising dramatically. This possibly an effect immune modulations chemotherapeutic drugs that raises resistance. Among list, IL-6 IL-17 are host-derived paradoxical effectors attune responses in malignant lung cells. Their excessive release cytokine milieu stabilizes immunosuppressive phenotypes, resulting cellular perturbations. During tumor development, significance these molecules reflected their potential regulate oncogenesis by initiating a myriad signaling events influence growth metastatic ability benign Moreover, transactivation contributes antiapoptotic mechanisms favors cell survival via constitutive expression immunoregulatory molecules. Co-evolution gene duplication could be major drivers behind evolution, which have prompted generic changes and, hence, additive effect. The evolutionary model statistical analysis provide evidence about cytokines ancestral relationships site-specific conservation, more convincing as both share cysteine-knot-like structures important maintaining structural integrity. Funneling through findings help find residues serve catalytic role functioning. Designing peptides or subunit vaccine formulations against those conserved aid combating pathogenesis.

Language: Английский

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Biomarkers of success of anti-PD-(L)1 immunotherapy for non-small cell lung cancer derived from RNA- and whole-exome sequencing: results of a prospective observational study on a cohort of 85 patients

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 11, 2024

Immune checkpoint inhibitors (ICIs) treatment have shown high efficacy for about 15 cancer types. However, this therapy is only effective in 20-30% of patients. Thus, the precise biomarkers ICI response are an urgent need.

Language: Английский

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