Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC).
Methods: A CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score.
Results: Three CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts.
Conclusions: This study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458312 | PMC |
| http://dx.doi.org/10.1136/jitc-2021-002671 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CD68 as a multi-omic prognostic biomarker in digestive system cancers: correlations with tumor-infiltrating immune cells and immune checkpoints.
Front Immunol
September 2025
Department of Digestion, Huaihe Hospital of Henan University, Kaifeng, China.
Background And Objective: CD68 plays a crucial role in promoting phagocytosis. However, its expression level, prognostic value and the correlations with tumor-infiltrating immune cells (TIICs) or common tumor immune checkpoints (TICs) in human digestive system cancers (DSC) remain poorly understood. This study aims to investigate the expression levels, prognostic significance, and clinical implications of CD68, as well as its correlations with six TIICs and four common TICs in DSC.
View Article and Find Full Text PDFTertiary lymphoid structures correlate with the therapeutic efficacy and prognosis of resectable esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy plus immunotherapy.
Front Immunol
September 2025
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Background: Tertiary lymphoid structures (TLSs) are linked to prognosis in esophageal squamous cell carcinoma (ESCC), but whether the distribution, abundance, and maturity of TLSs affect therapeutic efficacy and prognosis in ESCC treated with neoadjuvant chemoradiotherapy plus immunotherapy (NRCI) remains unclear. We explored TLS characteristics and correlated them with patient survival.
Methods: A total of 157 resectable ESCC patients treated with neoadjuvant therapy between September 2020 and May 2023 were divided into NRCI (n=49) and neoadjuvant chemoimmunotherapy (NCI, n=108) groups.
KPNA2 Expression as a Biomarker for Immunosuppressive Microenvironment Predicting Response to TKI and Immunotherapy in Metastatic Renal Cell Carcinoma.
Eur J Pharmacol
September 2025
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:
Background: Immunotherapy (IO) combined with tyrosine kinase inhibitors (TKI) are now first-line therapy for advanced renal cell carcinoma (RCC), though reliable predictive biomarkers remain elusive. Recent evidence demonstrates that karyopherin α2 subunit (KPNA2), a nuclear transport regulator, plays key roles in tumorigenesis and therapy resistance.
Methods: Two cohorts were analyzed: an institutional cohort of metastatic RCC patients (ZS-MRCC) and the phase III JAVELIN Renal 101 trial cohort.
Multifunctional Hybrid Membrane-Coated Nanomotors for Magnetically Guided, Cascade-Activated Chemoimmunotherapy for Triple-Negative Breast Cancer.
ACS Appl Mater Interfaces
September 2025
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China.
Here, we report a multifunctional hybrid membrane-coated nanomotor for cancer chemoimmunotherapy, which consists of mesoporous silica-coated iron oxide nanoparticles (MF) as a drug carrier, loaded with doxorubicin (DOX), l-arginine (l-arg), and glucose oxidase (GOx), and camouflaged with a hybrid of red blood cell membranes (mRBC) and cancer cell membranes (CCM). RM-GDL-MF has a cascade of catalytic reactions, where glucose is catalyzed by GOx to produce HO, and l-arg is oxidized by the produced HO to release nitric oxide (NO), leading to self-propelled motion in order to promote the penetration of the extracellular matrix (ECM) in the tumor. The hybrid membrane provides not only stealth properties from mRBC to evade immune clearance but also tumor-orientation ability to target the tumor from the CCM.
View Article and Find Full Text PDFImmunoprofiling at an Institutional Scale Reveals That High Numbers of Intratumoral CD8 and PD-1 Cells Predict Superior Patient Survival Across Major Cancer Types Independent of Major Risk Factors.
JCO Precis Oncol
September 2025
Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA.
Purpose: Retrospective studies have found associations between the number of intratumoral immune cells and patient outcomes for specific cancers treated with targeted therapies. However, the clinical value of routinely quantifying intratumoral immune biomarkers using a digital pathology platform in the pan-cancer setting within an active clinical laboratory has not been established.
Methods: We developed ImmunoProfile, a daily clinical workflow that integrates automated multiplex immunofluorescence tissue staining, digital slide imaging, and machine learning-assisted scoring to quantify intratumoral CD8, PD-1, CD8PD-1, and FOXP3 immune cells and PD-L1 expression in formalin-fixed, paraffin-embedded tissue samples in a standardized and reproducible manner.