ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Immune Marker Spatial Distribution and Clinical Outcome after PD-1 Blockade in Mismatch Repair-deficient, Advanced Colorectal Carcinomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan.Cell reports. Medicine · 2025Trial
- Evaluation of CD3 and CD8 T-Cell Immunohistochemistry for Prognostication and Prediction of Benefit From Adjuvant Chemotherapy in Early-Stage Colorectal Cancer Within the QUASAR Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Computational Modeling of Cellular Influence Delineates Functionally Relevant and Distinct Cellular Neighborhoods in Primary and Metastatic Pancreatic Ductal Adenocarcinoma.Cancer immunology research · 2026Article
- Radiomic features of CECT and SUVmax of dual-tracer PET/CT reveal PD-L1 spatial heterogeneity in PDAC.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Myeloid-derived PD-L1 characterizes spatially organized immune architecture in colorectal cancer.Frontiers in immunology · 2026Article
- STK25 Loss Augments Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Stability in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Spatially resolved C1QCCell discovery · 2025Article
- Spatially Resolved, Multiregion Proteomics for Prediction of Immunotherapy Outcome in Deficient Mismatch Repair Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- A PET-CT radiomics model for immunotherapy response and prognosis prediction in patients with metastatic colorectal cancer.Frontiers in oncology · 2025Article
- The immunosuppressive role of CCR8Journal of Cancer · 2025Article
- Article
- Recent developments in immunotherapy for gastrointestinal tract cancers.Journal of hematology & oncology · 2024Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTargeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) interaction has led to durable responses in fewer than half of patients with mismatch repair-deficient (MMR-d) advanced colorectal cancers. Immune contexture, including spatial distribution of immune cells in the tumor microenvironment (TME), may predict immunotherapy outcome. EXPERIMENTAL
designImmune contexture and spatial distribution, including cell-to-cell distance measurements, were analyzed by multiplex immunofluorescence (mIF) in primary colorectal cancers with d-MMR (N = 33) from patients treated with anti-PD-1 antibodies. By digital image analysis, density, ratio, intensity, and spatial distribution of PD-L1, PD-1, CD8, CD3, CD68, LAG3, TGFβR2, MHC-I, CD14, B2M, and pan-cytokeratin were computed. Feature selection was performed by regularized Cox regression with LASSO, and a proportional hazards model was fitted to predict progression-free survival (PFS).
resultsFor predicting survival among patients with MMR-d advanced colorectal cancer receiving PD-1 blockade, cell-to-cell distance measurements, but not cell densities or ratios, achieved statistical significance univariately. By multivariable feature selection, only mean number of PD-1+ cells within 10 μm of a PD-L1+ cell was significantly predictive of PFS. Dichotomization of this variable revealed that those with high versus low values had significantly prolonged PFS [median not reached (>83 months) vs. 8.5 months (95% confidence interval (95% CI), 4.7-NR)] with a median PFS of 28.4 months for all patients [adjusted HR (HRadj) = 0.14; 95% CI, 0.04-0.56; P = 0.005]. Expression of PD-1 was observed on CD8+ T cells; PD-L1 on CD3+ and CD8+ T lymphocytes, macrophages (CD68+), and tumor cells.
conclusionsIn d-MMR colorectal cancers, PD-1+ to PD-L1+ receptor to ligand proximity is a potential predictive biomarker for the effectiveness of PD-1 blockade.
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