ArticleThe journal of pathology. Clinical research2021
Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.
Article in The journal of pathology. Clinical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- WNT signalling promotes NF-κB activation and drug resistance in KRAS-mutant colorectal cancer.EMBO reports · 2025Article
- Histopathology-based assessment of the tumour microenvironment in gastrointestinal cancers: practical approaches to prognostication and treatment stratification.The journal of pathology. Clinical research · 2025Review
- IL6 and IL6R as Prognostic Biomarkers in Colorectal Cancer.Biomolecules · 2024Article
- TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer.Translational oncology · 2024Article
- PTOV1 facilitates colorectal cancer cell proliferation through activating AKT1 signaling pathway.Heliyon · 2024Article
- The Glasgow Microenvironment Score: an exemplar of contemporary biomarker evolution in colorectal cancer.The journal of pathology. Clinical research · 2024Review
- Histopathological tumour microenvironment score independently predicts outcome in primary operable colorectal cancer.The journal of pathology. Clinical research · 2024Article
- Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.Expert reviews in molecular medicine · 2024Review
- A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis.Current therapeutic research, clinical and experimental · 2024Review
- LAG3 in gastric cancer: it's complicated.Journal of cancer research and clinical oncology · 2023Article
- Vista of the Future: Novel Immunotherapy Based on the Human V-Set Immunoregulatory Receptor for Digestive System Tumors.International journal of molecular sciences · 2023Review
- Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival.Frontiers in oncology · 2023Article
- PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer-Its Clinical and Biological Significance in Immune Microenvironment.International journal of molecular sciences · 2022Article
- New Potential Immune Biomarkers in the Era of Precision Medicine: Lights and Shadows in Colorectal Cancer.Life (Basel, Switzerland) · 2022Review
- Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.Cell communication and signaling : CCS · 2022Review
- HAMP as a Prognostic Biomarker for Colorectal Cancer Based on Tumor Microenvironment Analysis.Frontiers in oncology · 2022Article
- The Role of Tumor Microenvironment and Immune Response in Colorectal Cancer Development and Prognosis.Pathology oncology research : POR · 2022Review
- Lag3: From Bench to Bedside.Cancer treatment and research · 2022Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM-3, LAG-3 and PD-1 in patients with stage I-III colorectal cancer. Immunohistochemistry was employed to detect TIM-3, LAG-3, PD-1 and PD-L1 in 773 patients with stage I-III colorectal cancer. Immune checkpoint protein expression was assessed in tumour cells using the weighted histoscore, and in immune cells within the stroma using point counting. Scores were analysed for associations with survival and clinical factors. High tumoural LAG-3 (hazard ratio [HR] 1.45 95% confidence interval [CI] 1.00-2.09, p = 0.049) and PD-1 (HR 1.34 95% CI 1.00-1.78, p = 0.047) associated with poor survival, whereas high TIM-3 (HR 0.60 95% CI 0.42-0.84, p = 0.003), LAG-3 (HR 0.58 95% CI 0.40-0.87, p = 0.006) and PD-1 (HR 0.65 95% CI 0.49-0.86, p = 0.002) on immune cells within the stroma associated with improved survival, while PD-L1 in the tumour (p = 0.487) or the immune cells within the stroma (p = 0.298) was not associated with survival. Furthermore, immune cell LAG-3 was independently associated with survival (p = 0.017). Checkpoint expression scores on stromal immune cells were combined into a Combined Immune Checkpoint Stromal Score (CICSS), where CICSS 3 denoted all high, CICSS 2 denoted any two high, and CICSS 1 denoted other combinations. CICSS 3 was associated with improved patient survival (HR 0.57 95% CI 0.42-0.78, p = 0.001). The results suggest that individual and combined high expression of TIM-3, LAG-3, and PD-1 on stromal immune cells are associated with better colorectal cancer prognosis, suggesting there is added value to investigating multiple immune checkpoints simultaneously.
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