Dataset Information

Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women.

ABSTRACT: Background: 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.Methods: 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.Results: CTL and GZMB composite scores were positively correlated (r = 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 BRAF mutation status. HRs (95% CI) were 0.53 (0.38-0.75; Ptrend = 0.0004) and 0.66 (0.51-0.86; Ptrend = 0.002) for all-cause death, respectively, and 0.30 (0.18-0.51; Ptrend < 0.0001) and 0.41 (0.27-0.63; Ptrend < 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.Conclusions: Higher tumor infiltration with CTL and GZMB cells is associated with improved all-cause and cancer-specific survival of colorectal cancer patients.Impact: Both the number of CTLs and GZMB appear to be useful prognostic factors in colorectal cancer, irrespective of stage. Cancer Epidemiol Biomarkers Prev; 26(4); 622-31. ©2016 AACR.

SUBMITTER: Prizment AE

PROVIDER: S-EPMC5380516 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women.

Prizment Anna E AE Vierkant Robert A RA Smyrk Thomas C TC Tillmans Lori S LS Nelson Heather H HH Lynch Charles F CF Pengo Thomas T Thibodeau Stephen N SN Church Timothy R TR Cerhan James R JR Anderson Kristin E KE Limburg Paul J PJ

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20161215 4

<b>Background:</b> 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.<b>Methods:</b> Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (f ...[more]

PMID: 27979806

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Project description:BACKGROUND: The purpose of this study was to estimate the relative impact of changes in demographics, stage at detection, treatment mix, and medical technology on 5-year survival among older colorectal cancer (CRC) patients. METHODS: We selected older patients diagnosed with CRC between 1992 and 2000 from the SEER-Medicare database and followed them through 2005. Trends in demographic characteristics, stage at detection and initial treatment mix were evaluated descriptively. Separate multivariate logistic regression models for colon (CC) and rectal cancer (RC) patients were estimated to isolate the independent effects of these factors along with technological change (proxied by cohort year) on 5-year survival. RESULTS: Our sample included 37,808 CC and 13,619 RC patients (combined mean +/- SD age: 77.2 +/- 7.0 years; 55% female; 87% white). In recent years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV, and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC and RC patients diagnosed in later years were slightly older with somewhat better Charlson scores and were more likely to be female, from the Northeast, and from areas with higher average education levels. Surgery alone was more common in later years for CC patients while combined surgery, chemotherapy, and radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to 42.2% for RC patients. Multivariate logistic regressions indicate that patients diagnosed in 2000 had significantly greater odds of 5-year survival than those diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC). Our decomposition suggests that early detection had little impact on survival; rather, technological improvements (e.g., new medical technologies or more effective use of existing technologies) and changing demographics were responsible for the largest share of the change in 5-year survival in CC and RC between 1992 and 2000. CONCLUSION: Technological advances and changes in patient demographics had the largest impact on improved colorectal cancer survival during the study period.

Project description:BACKGROUND:Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients. METHODS:Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes. RESULTS:In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, "immunoregulatory interactions between a lymphoid and non-lymphoid cell", that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~?70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival. CONCLUSIONS:Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.

Project description:BackgroundDairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest.MethodsWe analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses' Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty.ResultsDuring follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty.ConclusionsThe results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk.

Dataset Information

Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women.

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Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women.

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