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Record W3016572530 · doi:10.7554/elife.53244

Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma

2020· article· en· W3016572530 on OpenAlexafffund
Kenji Murata, Munehide Nakatsugawa, Muhammed A. Rahman, Linh T. Nguyen, Douglas G. Millar, David T. Mulder, Kenji Sugata, Hiroshi Saijo, Yukiko Matsunaga, Yuki Kagoya, Tingxi Guo, Mark Anczurowski, Chung-Hsi Wang, Brian D. Burt, Dalam Ly, Kayoko Saso, Alexandra Easson, David P. Goldstein, Michael Reedijk, Danny Ghazarian, Trevor J. Pugh, Marcus O. Butler, Tak W. Mak, Pamela S. Ohashi, Naoto Hirano

Bibliographic record

VenueeLife · 2020
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsOntario Institute for Cancer ResearchUniversity of TorontoPrincess Margaret Cancer CentreUniversity Health Network
FundersJapan Society for the Promotion of SciencePrincess Margaret Cancer FoundationNatural Sciences and Engineering Research Council of CanadaMitacsTerry Fox Research InstituteOntario Institute for Cancer Research
KeywordsEpitopeHuman leukocyte antigenAntigenBiologyAlleleImmunotherapyTumor-infiltrating lymphocytesImmunologyCancer immunotherapyT-cell receptorMelanomaT cellImmune systemGeneCancer researchGenetics

Abstract

fetched live from OpenAlex

HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.059
Threshold uncertainty score0.576

Codex and Gemma teacher scores by category

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

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 head0.036
GPT teacher head0.276
Teacher spread0.240 · 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 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

Citations24
Published2020
Admission routes2
Has abstractyes

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