Journal article
Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women
Cancer epidemiology, biomarkers & prevention, Vol.26(4), pp.622-631
04/2017
DOI: 10.1158/1055-9965.EPI-16-0641
PMCID: PMC5380516
PMID: 27979806
Abstract
Host immune response may predict the course of colorectal cancer. We examined the survival of 468 colorectal cancer patients associated with two tumor-infiltrating immune biomarkers, the number of cytotoxic T lymphocytes (CTLs), and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study.
Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies. We scored CTL and GZMB densities in tumor epithelial and stromal tissues and also created a composite score for each biomarker (sum of the scores across tissue compartments). Cox regression estimated the HR and 95% confidence intervals (CI) for all-cause and colorectal cancer-specific death associated with each composite score.
CTL and GZMB composite scores were positively correlated (
= 0.65) and each biomarker was inversely correlated with stage at diagnosis. Both composite scores were higher in proximal colon tumors and tumors characterized by MSI-high, CIMP-high, or
mutation status. HRs (95% CI) were 0.53 (0.38-0.75;
= 0.0004) and 0.66 (0.51-0.86;
= 0.002) for all-cause death, respectively, and 0.30 (0.18-0.51;
< 0.0001) and 0.41 (0.27-0.63;
< 0.0001) for colorectal cancer-related death, respectively. Including CTL and GZMB scores simultaneously in the model significantly improved the predictive performance of the models for all-cause and colorectal cancer-related death.
Higher tumor infiltration with CTL and GZMB cells is associated with improved all-cause and cancer-specific survival of colorectal cancer patients.
Both the number of CTLs and GZMB appear to be useful prognostic factors in colorectal cancer, irrespective of stage.
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Details
- Title: Subtitle
- Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women
- Creators
- Anna E Prizment - University of Minnesota Masonic Cancer Center, Minneapolis, MinnesotaRobert A Vierkant - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MinnesotaThomas C Smyrk - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaLori S Tillmans - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaHeather H Nelson - University of Minnesota Masonic Cancer Center, Minneapolis, MinnesotaCharles F Lynch - Department of Epidemiology, University of Iowa, Iowa City, IowaThomas Pengo - University Imaging Centers, University of Minnesota, Minneapolis, MinnesotaStephen N Thibodeau - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaTimothy R Church - Division of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, MinnesotaJames R Cerhan - Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MinnesotaKristin E Anderson - University of Minnesota Masonic Cancer Center, Minneapolis, MinnesotaPaul J Limburg - Division of Gastroenterology & Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.26(4), pp.622-631
- DOI
- 10.1158/1055-9965.EPI-16-0641
- PMID
- 27979806
- PMCID
- PMC5380516
- NLM abbreviation
- Cancer Epidemiol Biomarkers Prev
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Publisher
- United States
- Grant note
- R01 CA107333 / NCI NIH HHS HHSN261201000032C / NCI NIH HHS UL1 TR000114 / NCATS NIH HHS P30 CA086862 / NCI NIH HHS P30 CA015083 / NCI NIH HHS R01 CA039742 / NCI NIH HHS
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Epidemiology
- Record Identifier
- 9983995182202771
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