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Record W4403222422 · doi:10.1158/2326-6066.cir-23-0639

Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells

2024· article· en· W4403222422 on OpenAlexafffund
Li Deng, Scott R. Walsh, Andrew Nguyen, Jordon M. Inkol, Michael J. Westerveld, Lan Chen, Nader El-Sayes, Karen Mossman, Samuel T. Workenhe, Yonghong Wan

Bibliographic record

VenueCancer Immunology Research · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsUniversity of GuelphMcMaster UniversityMcMaster University Medical Centre
FundersCanadian Institutes of Health Research - Antimicrobial Resistance Research InitiativeTerry Fox Research InstituteCanadian Cancer Society
KeywordsImmunogenicityCD8Cancer immunotherapyImmunotherapyT cellCancerCytotoxic T cellAntigenCancer researchBiologyImmunologyT-cell receptorImmune systemIn vitroGenetics

Abstract

fetched live from OpenAlex

Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T-cell responses induced toward several distinct neoantigen targets to regress MC38 tumors. Despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. Although unable to kill tumor cells, T cells showed robust killing capacity toward neoantigen peptide-loaded cells. Tumor-cell killing was rescued by saturation of target peptide-loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full antitumor effect of cancer vaccines.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.276
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.102
GPT teacher head0.374
Teacher spread0.272 · 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.

Study designBench or experimental
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

Citations4
Published2024
Admission routes2
Has abstractyes

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