ArticleThe American journal of pathology1999
High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability.
Article in The American journal of pathology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
222 citing papers in PubMed, 3 syntheses or guidelines pooled it, 475 citations in OpenAlex.
- Inflammatory markers for predicting overall survival in gastric cancer patients: A systematic review and meta-analysis.PloS one · 2020Pooled it
- Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence.Frontiers in oncology · 2019Pooled it
- Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival.Genome research · 2014Pooled it
- Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial.Journal for immunotherapy of cancer · 2021Trial
- Early postoperative controlling nutritional status (CONUT) score is associated with complication III-V after hepatectomy in hepatocellular carcinoma: A retrospective cohort study of 1,334 patients.Scientific reports · 2018Trial
- Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.Science (New York, N.Y.) · 2017Trial
- PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.The New England journal of medicine · 2015Trial
- Detection of MSI signals from peripheral blood for monitoring response to immune checkpoint blockade therapy in patients with advanced microsatellite-unstable gastrointestinal cancers: A pilot study.International journal of cancer · 2026Article
- Significance of tumor infiltrating granulocytes and neutrophil extracellular traps in colorectal cancer.British journal of cancer · 2026Article
- Tumour immune contexture and immune evasion in sporadic and Lynch syndrome-associated microsatellite unstable colorectal cancers.British journal of cancer · 2026Article
- Harnessing biomarkers to guide immunotherapy in esophageal cancer: toward precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- T-cell Subset Features and Distributions Evolve across the Colorectal Precancer-Cancer Spectrum.Cancer immunology research · 2026Article
- Pseudomonas aeruginosa induces tumor pyroptosis and immune activation to enhance checkpoint blockade in colorectal cancer.Cancer immunology, immunotherapy : CII · 2026Article
- The Utility of Tissue-Agnostic Drugs in Lung Cancer Treatment.Pharmaceutical medicine · 2025Review
- Unveiling MMR deficiency in pediatric and AYA high-grade gliomas: insights from multiomic profiling.Journal of neuro-oncology · 2025Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- The efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy for locally advanced gastric cancer: a single-center, real-world clinical study.Cancer immunology, immunotherapy : CII · 2025Article
- Phenotypic attributes and survival in mismatch repair deficient/microsatellite instability-high colorectal carcinomas.World journal of clinical oncology · 2025Article
- Nivolumab-induced subacute cutaneous lupus erythematosus in a patient with sigmoid colon cancer: a case report and review of the literature.Frontiers in oncology · 2025Article
- DNA repair-dependent immunogenic liabilities in colorectal cancer: opportunities from errors.British journal of cancer · 2024Review
162 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microsatellite instability (MSI) characterizes colorectal carcinomas (CRCs) in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and a proportion of sporadic CRCs. These MSI+ CRCs share several clinicopathological features, including a reputation for better survival rates than MSI- cases and a pronounced stromal inflammatory reaction of still undefined nature. In the present study, the presence, spatial distribution, and activation status of infiltrating cytotoxic effectors were investigated comparatively in 18 MSI+ and 37 MSI- CRCs by immunohistochemistry. The frequency of apoptosis was also evaluated by morphology and in situ end-labeling. MSI+ cases carried significantly higher numbers of cytotoxic lymphocytes infiltrating within neoplastic epithelial structures, as shown by immunostaining for CD3 (15.1 +/- 6.2 versus 4.6 +/- 4.1, P < 0.001), CD8 (13 +/- 6.4 versus 3.7 +/- 3.8, P < 0.001), and TIA-1 (11.2 +/- 6.5 versus 1.9 +/- 1.7, P < 0.001). These cytotoxic effectors were globally more activated in MSI+ than in MSI- tumors, as revealed by the expression of granzyme B (5.3 +/- 4.5 versus 0.6 +/- 1.3, P < 0.001). In MSI+ CRCs, the number of intraepithelial activated cytotoxic lymphocytes was significantly correlated with the proximal location of the tumor, a poorly differentiated phenotype, and the presence of peritumor lymphoid nodules. Multivariate analysis revealed that MSI was the major determinant of the presence of activated cytotoxic intraepithelial lymphocytes. Moreover, MSI+ CRCs also showed a significantly higher percentage of tumor cells undergoing apoptotic cell death (4.1 +/- 2.1 versus 2.6 +/- 1.1, P < 0.0001, by the TUNEL method), often located in close proximity of activated cytotoxic lymphocytes. These results are consistent with the presence of anti-tumor cytotoxic immune responses in most of MSI+ CRCs, a phenomenon that may at least in part contribute to the survival advantage ascribed to these patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.