ArticleAnnals of surgical oncology2018
Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer.
Article in Annals of surgical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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119 citing papers in PubMed, 181 citations in OpenAlex.
- Perforin and Granulysin-Mediated Cytotoxicity in Colorectal Cancer Patients.Medicina (Kaunas, Lithuania) · 2026Article
- Germinal Center-Like Tertiary Lymphoid Structures Mark Immune Responsiveness and Enable Checkpoint Immunotherapy in Bladder Cancer.Oncology research · 2026Article
- ESR1 Expression Negatively Correlates with Immune Cell Infiltration and Response to Immune Checkpoint Inhibitors in Estrogen Receptor-Positive/HER2-Negative Breast Cancer.Annals of surgical oncology · 2026Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- IC2Bert: masked gene expression pretraining and supervised fine tuning for robust immune checkpoint blockade (ICB) response prediction.Scientific reports · 2025Article
- Construction of an immune prediction model for osteosarcoma based on coagulation-related genes.Discover oncology · 2025Article
- Personalized risk stratification in colorectal cancer via PIANOS system.Nature communications · 2025Article
- NKG7 is a Stable Marker of Cytotoxicity Across Immune Contexts and Within the Tumor Microenvironment.European journal of immunology · 2025Article
- The American Joint Committee on Cancer (AJCC) Breast Cancer Staging, Eighth Edition, is more Reflective of Cancer Biology than the Seventh Edition.Annals of surgical oncology · 2025Article
- STAT3/TGFBI signaling promotes the temozolomide resistance of glioblastoma through upregulating glycolysis by inducing cellular senescence.Cancer cell international · 2025Article
- Comprehensive Analysis of Granzymes and Perforin Family Genes in Multiple Cancers.Biomedicines · 2025Article
- Identification of Biomarkers Based on Starvation Response-Related Genes for Assessing the Immune Profile and Prognosis in Lung Adenocarcinoma.International journal of genomics · 2025Article
- The landscape and clinical impact of tumor-associated macrophages and PD-L1 in primary breast cancers and their brain metastases.Frontiers in immunology · 2025Article
- Comparative analysis of tertiary lymphoid structures for predicting survival of colorectal cancer: a whole-slide images-based study.Precision clinical medicine · 2024Article
- A patient stratification signature mirrors the immunogenic potential of high grade serous ovarian cancers.Journal of translational medicine · 2024Article
- Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook.Biomolecules · 2024Review
- LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer.BMC immunology · 2024Article
- Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.Communications biology · 2024Article
- Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction.iScience · 2024Article
- Emerging measurements for tumor-infiltrating lymphocytes in breast cancer.Japanese journal of clinical oncology · 2024Review
59 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundElevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity.
methodsGenomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA). CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition.
resultsHigh CYT was associated with high microsatellite instability (MSI-H), as well as high levels of activated memory CD4+T cells, gamma-delta T cells, and M1 macrophages. CYT-high CRC patients had improved overall survival (p = 0.019) and disease-free survival (p = 0.016) compared with CYT-low CRC patients, especially in TIL-positive tumors. Multivariate analysis demonstrated that CYT- high associates with improved survival independently after controlling for age, lymphovascular invasion, colonic location, microsatellite instability, and TIL positivity. The levels of immune checkpoint molecules (ICMs)-programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), T cell immunoglobulin and mucin domain 3 (TIM3), and indoleamine 2,3-dioxygenase 1 (IDO1)-correlated significantly with CYT (p < 0.0001); with improved survival in CYT-high and ICM-low patients, and poorer survival in ICM-high patients.
conclusionsHigh CYT within CRC is associated with improved survival, likely due to increased immunity and cytolytic activity of T cells and M1 macrophages. High CYT is also associated with high expression of ICMs; thus, further studies to elucidate the role of CYT as a predictive biomarker of the efficacy of immune checkpoint blockade are warranted.
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