Circulating Immune Cell Composition and Cancer Risk: A Prospective Study Using Epigenetic Cell Count Measures

Cornet, Charlotte Le; Schildknecht, Konstantin; Chornet, Araceli Rossello; Fortner, Renée T.; Maldonado, Sandra González; Katzke, Verena; Kühn, Tilman; Johnson, Theron; Olek, Sven; Kaaks, Rudolf

doi:10.1158/0008-5472.can-19-3178

Cited by 20 publications

(21 citation statements)

References 41 publications

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“…However, recent data highlighted the key role of the immune system in cancer protection (31) and among cancer immunity effector cells, CD8+ Tcells were identified as having a major role (32). Thus, in the study conducted by Le cornet et al on healthy individuals, significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer, whereas a significant positive association was observed between relative counts of FOXP3+ regulatory T-cells (Tregs) and lung cancer risk (31). CD8+ T-cell counts are elevated during HIV infection and do not normalize despite long-term ART with sustained undetectable HIV viral load (33).…”

Section: Discussionmentioning

confidence: 99%

Spectrum and Incidence Trends of AIDS- and Non–AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort

Poizot‐Martin

Lions

Allavena³

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Cancer risk is higher in people living with HIV (PLWH) compared with the general population, and cancers related to age are expected to be most prevalent. Methods: We determined the spectrum and incidence rates of AIDS-defining cancers (ADC) and non–AIDS-defining cancers (NADC) and of lung, Hodgkin lymphoma (HL), head and neck (HNC), colon–rectum, anal, liver, breast, prostate, and urinary bladder cancers between January 2010 and December 2015 in the French Dat'AIDS cohort. Incidence rates were calculated by year and compared using the χ2 test for linear trend. Standardized incidence ratios [SIR (95% confidence interval)] were calculated relative to the French general population. Results: Among 44,642 patients, corresponding to 180,216.4 person-years (PY), 1,440 cancer cases occurred in 1,314 patients. ADC incidence was 191.4 (172.3–212.7)/105 PY and declined over time overall and in men, whereas NADC incidence was higher [548.8 (515.6–584.1)/105 PY] and did not change. In men, non-Hodgkin lymphoma was the most common cancer, but prostate cancer had the highest incidence among NADCs. Breast cancer was the most common cancer in women. SIRs were higher for cervical cancer [1.93 (1.18–3.14)], HNC in women [2.4 (1.4–4.2)], liver [overall: 3.8 (3.1–4.6); men: 3.2 (2.5–4.0); women: 12.9 (8.3–20.0)], and HL [overall: 13.8 (11.1–17.1); men: 16.2 (12.9–20.4); women: 6.2 (3.22–11.9)] but lower for lung [overall: 0.7 (0.6–0.9); men: 0.7 (0.5–0.8)], prostate [0.6 (0.5–0.7)], and breast cancers [0.6 (0.4–0.7)]. Conclusions: Spectrum of NADCs has changed, with prostate and breast cancers becoming the most common despite their lower SIR. Impact: These results confirm the need to maintain regular epidemiologic cancer monitoring in order to update screening guidelines.

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Section: Discussionmentioning

confidence: 99%

Spectrum and Incidence Trends of AIDS- and Non–AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort

Poizot‐Martin

Lions

Allavena³

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Relative counts of immune cells in genomic DNA extracted from buffy coats were assessed by quantitative real-time PCR assisted cell counting (qPACC). Descriptions of the laboratory methods are given on the Epiontis web site (http://www.epiontis.com), have been previously published (13,14,(17)(18)(19), and are detailed in the Supplementary Methods and Materials M1 to M4. In brief, for each subject, 1.5µg of genomic DNA bisulfite treated prior to qPCR analysis.…”

Section: Laboratory Methods: Quantification Of Immune Cellsmentioning

confidence: 99%

“…Risk associations were examined for neutrophils and overall CD3+ T cells (Model 1), as well as in a series of nested models. Stepwise de-composition models were fitted within the re-calibrated T-cells, breaking down total T-lymphocytes (CD3+) into its CD8+ (cytotoxic) and CD4+ (helper cell) sub-fractions (Model 2), and CD4+ into its FOXP3+ (regulatory) and FOXP3-(non-regulatory) sub-fractions (Model 3) (14). In this stepwise de-composition approach, log-likelihood ratio tests were used to examine improvements in overall model fit.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…This type of assay can be applied to DNA extracted from frozen, non-intact white blood cells as well as other tissues. By applying this method to stored buffy coat samples of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, we found that higher counts of FOXP3+ (regulatory) T-cell relative to total nucleated cells were associated with higher risks of cancers of the lung, colorectum and breast, whereas lower relative CD8+ (cytotoxic) T-cells counts were inversely associated with lung and breast cancer risks (14). By contrast, this first study showed no associations of cancer risk with relative counts of monocytes, B-cells or natural killer cells, and only marginally suggestive associations (non-significant) for neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures

Katzke

Cornet

Mahfouz³

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing. Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale. Results: Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. Conclusions: These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. Impact: We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development. See related commentary by Michaud and Kelsey, p. 2176

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“…However, to our knowledge it has not been adapted to analyze urinary cell populations in AR, making this the first trial to apply epigenetic qPCR analysis of urinary cells in patients with graft deterioration. The epigenetic qPCR is an established method for quantifying immune cells in blood or tissues and was used in different studies before (28,29). Here, this method was applied in addition to FC to validate our findings with a complementary method.…”

Section: Epigenetic Qpcr Analyses Qualitatively Confirmed T Cell and ...mentioning

confidence: 98%

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection

Grothgar

Goerlich

Samans³

et al. 2022

Front. Med.

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Early detection of kidney transplant (KT) rejection remains a challenge in patient care. Non-invasive biomarkers hold high potential to detect rejection, adjust immunosuppression, and monitor KT patients. So far, no approach has fully satisfied requirements to innovate routine monitoring of KT patients. In this two-center study we analyzed a total of 380 urine samples. T cells and tubular epithelial cells were quantified in KT patients with graft deterioration using flow cytometry. Epigenetic urine cell quantification was used to confirm flow cytometric results. Moreover, a cohort of KT patients was followed up during the first year after transplantation, tracking cell subsets over time. Abundance of urinary cell counts differed in patients with and without rejection. Most strikingly, various T cell subsets were enriched in patients with T cell-mediated rejection (TCMR) compared to patients without TCMR. Among T cell subsets, CD8+HLA-DR+ T cells were most distinctive (AUC = 0.91, Spec.: 95.9%, Sens.: 76.5%). Epigenetic analysis confirmed T cell and tubular epithelial cell quantities as determined by flow cytometry. Urinary T cell abundance in new KT patients decreased during their first year after transplantation. In conclusion urinary T cells reflect intrarenal inflammation in TCMR. T cell subsets yield high potential to monitor KT patients and detect rejection. Hereby we present a promising biomarker to non-invasively diagnose TCMR.

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Circulating Immune Cell Composition and Cancer Risk: A Prospective Study Using Epigenetic Cell Count Measures

Abstract: The authors declare no conflict of interest Word count: 3994 Total number of figures and tables: 2 figures, 2 tables Supplemental Data and Methods: 1 figure, 5 tables Research.

Cited by 20 publications

References 41 publications

Spectrum and Incidence Trends of AIDS- and Non–AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort

Spectrum and Incidence Trends of AIDS- and Non–AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort

Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection

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