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Record W4391252891 · doi:10.1016/j.xcrm.2024.101393

Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer

2024· article· en· W4391252891 on OpenAlexaff
Matthew D. Galsky, Xiangnan Guan, Deepali Rishipathak, Aaron S. Rapaport, Hesham M. Shehata, Romain Banchereau, Kobe Yuen, Eugene Varfolomeev, Ruozhen Hu, Chia-Jung Han, Haocheng Li, Yuxin Liang, Domagoj Vucic, Li Wang, Jun Zhu, Haocheng Yu, Rebecca H. Herbst, Emma Hajaj, Evgeny Kiner, Aristotelis Bamias, Maria De Santis, Ian D. Davis, José Ángel Arranz, Eiji Kikuchi, Sandrine Bernhard, Patrick Williams, Chooi Lee, Ira Mellman, Shomyseh Sanjabi, Robert E. Johnston, Peter C. Black, Enrique Grande, Sanjeev Mariathasan

Bibliographic record

VenueCell Reports Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicBladder and Urothelial Cancer Treatments
Canadian institutionsUniversity of British ColumbiaRoche (Canada)
FundersNational Cancer InstituteF. Hoffmann-La Roche
KeywordsAtezolizumabCarboplatinCisplatinUrothelial cancerMedicineOncologyChemotherapyInternal medicineBladder cancerUrologyCancerImmunotherapyPembrolizumab

Abstract

fetched live from OpenAlex

In metastatic urothelial cancer (mUC), cisplatin versus carboplatin leads to durable disease control in a subset of patients. The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin as a potential explanation for these observations. Our findings indicate that improved outcomes with GemCis versus GemCarbo are primarily observed in patients with pretreatment tumors exhibiting features of restrained adaptive immunity. In addition, GemCis versus GemCarbo ± atezolizumab induces transcriptional changes in circulating immune cells, including upregulation of antigen presentation and T cell activation programs. In vitro experiments demonstrate that cisplatin, compared with carboplatin, exerts direct immunomodulatory effects on cancer cells, promoting dendritic cell activation and antigen-specific T cell killing. These results underscore the key role of immune modulation in cisplatin's efficacy in mUC and highlight the importance of specific chemotherapy backbones in immunotherapy combination regimens.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
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 head0.011
GPT teacher head0.285
Teacher spread0.274 · 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 source (direct Gemma or distilled Codex), 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

Citations54
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueCell Reports MedicineSame topicBladder and Urothelial Cancer TreatmentsFrench-language works237,207