ArticleOncotarget2015
Mismatch repair gene defects in sporadic colorectal cancer enhance immune surveillance.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Targeting DNA damage response to enhance cancer immunotherapy efficacy: molecular mechanisms and clinical advances.Medical oncology (Northwood, London, England) · 2025Pooled it
- Prognostic Value of Mismatch Repair Genes for Patients With Colorectal Cancer: Meta-Analysis.Technology in cancer research & treatment · 2018Pooled it
- High prevalence of unusual KRAS, NRAS, and BRAF mutations in POLE-hypermutated colorectal cancers.Molecular oncology · 2022Article
- MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.Prostate cancer and prostatic diseases · 2021Article
- Targeting the DNA damage response in immuno-oncology: developments and opportunities.Nature reviews. Cancer · 2021Review
- The role of immunogenic cell death in gastrointestinal cancer immunotherapy (Review).Biomedical reports · 2021Review
- CD80 expression is upregulated by TP53 activation in human cancer epithelial cells.Oncoimmunology · 2021Article
- MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer.Frontiers in molecular biosciences · 2021Article
- Therapeutic implications of germline genetic findings in cancer.Nature reviews. Clinical oncology · 2019Review
- Epithelial CD80 promotes immune surveillance of colonic preneoplastic lesions and its expression is increased by oxidative stress through STAT3 in colon cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Exploiting DNA repair defects in colorectal cancer.Molecular oncology · 2019Review
- Expression status of four mismatch repair proteins in patients with colorectal cancer: clinical significance in 1238 cases.International journal of clinical and experimental pathology · 2019Article
- CD39Oncotarget · 2018Article
- Intratumoral immune-biomarkers and mismatch repair status in leiyomyosarcoma -potential predictive markers for adjuvant treatment: a pilot study.Oncotarget · 2018Article
- Effects of immune suppression for transplantation on inflammatory colorectal cancer progression.Oncogenesis · 2018Article
- Single nucleotide polymorphisms inOncotarget · 2017Article
- Independent prognostic role of PD-L1expression in patients with esophageal squamous cell carcinoma.Oncotarget · 2017Article
- Construction and analysis of tissue microarrays in the era of digital pathology: a pilot study targeting CDX1 and CDX2 in a colon cancer cohort of 612 patients.The journal of pathology. Clinical research · 2017Article
- Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is evidence that colorectal cancers (CRC) with DNA mismatch repair deficiency (MMR-D) are associated with a better prognosis than the generality of large bowel malignancies. Since an active immune surveillance process has been demonstrated to influence CRC outcome, we investigated whether MMR-D can enhance the immune response in CRC. PATIENTS AND
methodsA group of 113 consecutive patients operated for CRC (42 stage I or II and 71 with stage III or IV) was retrospectively analyzed. The expression of MMR genes (MSH2, MLH1, MSH6 and PSM2) and co-stimulatory molecule CD80 was assessed by tissue microarray immunohistochemistry. In addition, tumor infiltrating mononuclear cells (TIMC) and T cell subpopulations (CD4, CD8, T-bet and FoxP-3) were quantified. The effect of specific siRNA (siMSH2, siMLH1, siMSH6 and siPSM2) transfection in HT29 on CD80 expression was quantified by flow cytometry. Non parametric statistics and survival analysis were used.
resultsPatients with MMR-D showed a higher T-bet/CD4 ratio (p = 0.02), a higher rate of CD80 expression and CD8 lymphocyte infiltration compared to those with no MMR-D. Moreover, in the MMR-D group, the Treg marker FoxP-3 was not expressed (p = 0.05). MMR-D patients with stage I or II and T-bet expression had a significant better survival (p = 0.009). Silencing of MSH2, MLH1 and MSH6, but not PSM2, significantly increased the rate of CD80+ HT29 cells (p = 0.007, p = 0.023 and p = 0.015, respectively).
conclusionsCRC with MMR-D showed a higher CD80 expression, and CD8+ and Th1 T-cell infiltration. In vitro silencing of MSH2, MLH1 and MSH6 significantly increased CD80+ cell rate. These results suggest an enhanced immune surveillance mechanism in presence of MMR-D.
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