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Associations between Calcium Intake and T-cell Infiltration in Colorectal Tumors

2025· article· en· W4410405326 on OpenAlexafffund
Evertine Wesselink, Claire E. Thomas, Yasutoshi Takashima, Hiroki Mizuno, Daniel D. Buchanan, Conghui Qu, Li Hsu, Andressa Dias Costa, Satoko Ugai, Yuxue Zhong, Jeroen R. Huyghe, Sushma Thomas, Steven Gallinger, Robert C. Grant, Loı̈c Le Marchand, Yohei Masugi, Fränzel J.B. van Duijnhoven, Tomotaka Ugai, Shuji Ogino, Jonathan A. Nowak, Ulrike Peters, Amanda I. Phipps

Bibliographic record

VenueCancer Prevention Research · 2025
Typearticle
Languageen
FieldMedicine
TopicVitamin D Research Studies
Canadian institutionsPrincess Margaret Cancer CentreLunenfeld-Tanenbaum Research InstituteUniversity Health Network
FundersOffice of Research Infrastructure Programs, National Institutes of HealthAmerican Cancer SocietyCancer Research UKNational Health and Medical Research CouncilBrigham and Women's HospitalNational Cancer InstituteNational Institutes of HealthOntario Research FoundationHarvard T.H. Chan School of Public HealthNational Heart, Lung, and Blood InstituteDivision of Loan RepaymentCanadian Institutes of Health Research
KeywordsStromal cellCD8CalciumColorectal cancerImmune systemInfiltration (HVAC)T cellMedicineFOXP3Internal medicineCD3PathologyBiologyEndocrinologyImmunologyCancer

Abstract

fetched live from OpenAlex

Higher T-cell infiltration in colorectal tumors has been associated with better prognosis. Evidence indicates that calcium signaling is essential for T-cell functioning. However, as it is unknown whether calcium intake influences T-cell infiltration, we investigated the association of calcium intake with T-cell subsets in the tumor microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumor-infiltrating T cells and calcium intake were available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and di-(4-amidinophenyl)-1H-indole-6-carboxamidine). Associations between prediagnostic calcium intake and densities of nonoverlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double-negative T-cell density in the epithelial (OR, 1.57; 95% confidence interval, 1.13-2.24) and stromal (OR, 1.24; 95% confidence interval, 1.06-1.45) tumor tissue areas. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double-negative T cells in the epithelial and stromal tumor tissue areas but not with the infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumor-immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research. PREVENTION RELEVANCE: Our research contributes to the understanding of how diet could influence immune cell infiltration in and around the tumor. Understanding which factors influence antitumor immune responses is of importance in the prevention of cancer recurrence and/or progression.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.022
Threshold uncertainty score0.324

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.095
GPT teacher head0.464
Teacher spread0.369 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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