ArticleBritish journal of cancer2013
The in situ local immune response, tumour senescence and proliferation in colorectal cancer.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Increased expression of Ki-67 is a poor prognostic marker for colorectal cancer patients: a meta analysis.BMC cancer · 2019Pooled it
- Senescence-associated gene signatures predict survival in lung cancer: a multi-cohort analysis.GeroScience · 2026Article
- Prognostic significance of a signature based on senescence-related genes in colorectal cancer.GeroScience · 2024Article
- The impact of the senescent microenvironment on tumorigenesis: Insights for cancer therapy.Aging cell · 2024Review
- Differences and Similarities between Colorectal Cancer Cells and Colorectal Cancer Stem Cells: Molecular Insights and Implications.ACS omega · 2023Article
- Association between Ki67 expression and therapeutic outcome in colon cancer.Oncology letters · 2023Article
- Cellular senescence in cancer: clinical detection and prognostic implications.Journal of experimental & clinical cancer research : CR · 2022Review
- High prevalence of p16 staining in malignant tumors.PloS one · 2022Article
- Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.The journal of pathology. Clinical research · 2021Article
- Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies.Cancers · 2020Review
- Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value.Open access Macedonian journal of medical sciences · 2018Article
- Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T Cell Immunity.Frontiers in oncology · 2018Review
- [Cellular senescence and colorectal cancer].Der Pathologe · 2017Review
- Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017Article
- Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer.Cancer science · 2017Article
- Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer.Oncotarget · 2016Article
- Clinical impact and network of determinants of tumour necrosis in colorectal cancer.British journal of cancer · 2016Article
- Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment.British journal of cancer · 2016Article
- Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis.British journal of cancer · 2015Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune cell infiltrates are important determinants of colorectal cancer (CRC) outcome. Their presence may be driven by tumour or host-specific factors. From previous studies in mice, senescence, a state of cell cycle arrest, may moderate tumour progression through upregulation of antitumour immune responses. The relationships between senescence and immune infiltrates have not previously been studied in humans. We explore whether a marker of senescence (p16(ink4a)) in combination with low level expression of a proliferation marker (ki-67) relate to T cell infiltrates in CRC, and whether p16(ink4a), Ki-67 and immune infiltrates have similar prognostic value.
methodsImmunostaining of p16(inka) and Ki-67 was performed within a CRC tissue microarray. Nuclear p16(inka) and Ki-67 were categorised as high/low. T-cell markers, CD3, CD45RO, CD8 and FOXP3 were scored separately as high/low grade in three areas of the tumour: the invasive margin (IM), tumour stroma and cancer cell nests (CCNs). results: Two hundred and thirty stage I-III cancers were studied. High nuclear p16(ink4a) was expressed in 63% and high proliferation (Ki-67 >15%) in 61%. p16(ink4a) expression was associated with reduced CD45RO+ cells at the IM (P<0.05) and within the stroma (P<0.05) and reduced CD8+ cells at the IM (P<0.01). A low Ki-67 proliferative index was associated with reduced density of CD3+ cells in CCNs (P<0.01), reduced CD45RO+ cells at the IM (P<0.05) and within the CCNs (P<0.001), reduced FOXP3+ cells at the IM (P<0.001), within the stroma (P=0.001) and within CCNs (P<0.001) and reduced CD8+ cells at the IM (P<0.05) and within the CCNs (P<0.05). Tumours with both a low proliferative index and expression of p16(ink4a) demonstrated similar consistent relationships with reduced densities of T-cell infiltrates. On multivariate analysis, TNM stage (P<0.001), low CD3 cells at the IM (P=0.014), low CD8 cells at the IM (P=0.037), low proliferation (Ki-67; P=0.013) and low senescence (p16(ink4a); P=0.002) were independently associated with poorer cancer survival.
conclusionSenescence, proliferation and immune cell infiltrates are independent prognostic factors in CRC. Although related to survival, p16(ink4a)-associated senescence is not associated with an upregulation of antitumour T-cell responses.
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