Evidence map›Paper›PMID 38068925›Full record

ArticleInternational journal of molecular sciences2023

Alterations in Intratumoral Immune Response before and during Early-On Nivolumab Treatment for Unresectable Advanced or Recurrent Gastric Cancer.

Yasuyoshi Sato, Hiroharu Yamashita, Yukari Kobayashi, Koji Nagaoka, Tetsuro Hisayoshi, Takuya Kawahara, Akihiro Kuroda, Noriyuki Saito, Ryohei Iwata, Yasuhiro Okumura and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. State-of-the-Art Cancer Immunotherapies.International journal of molecular sciences · 2024
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Yasuyoshi SatoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0003-4145-8694
Hiroharu YamashitaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yukari KobayashiDepartment of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0002-2600-2181
Koji NagaokaDepartment of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0001-8202-031X
Tetsuro HisayoshicBioinformatics, Inc., Chiyoda-ku, Tokyo 101-0052, Japan.
Takuya KawaharaClinical Research Promotion Center, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0002-3859-2756
Akihiro KurodaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Noriyuki SaitoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Ryohei IwataDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yasuhiro OkumuraDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Koichi YagiDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Susumu AikoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Sachiyo NomuraDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0003-4293-6205
Kazuhiro KakimiDepartment of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0003-2631-3040
Yasuyuki SetoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.ORCID 0000-0002-6953-8752
The University of Tokyo · JPUniversity of Tokyo Hospital · JPNihon University · JP

Funding

ONO Pharmaceutical co., ltd., and Bristol Myers Squibb 177100000920
6 · The paper itself

Abstract

We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR; objective response rate, OS; overall survival, PFS; progression-free survival) to previous trials. The immunograms of individual subjects displayed no significant changes before or early in the treatment, except for the regulatory T cell (Treg) score. Moreover, there were no consistent alterations observed among cases experiencing DCB. The intratumoral immune response was suppressed by previous treatments in most third- or later-line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in early-on-treatment tumors, but clonal replacement did not impact efficacy. High T cell/Treg ratios and a low UV-radiation-response gene signature were linked to DCB and treatment response. This study emphasizes the tumor immune response's importance in nivolumab efficacy for gastric cancer. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. The tumor-infiltrating immune response was compromised by prior treatments in third-line therapy, implying that, to enhance immunotherapeutic outcomes, commencing treatment at an earlier stage might be preferable. Larger cohort validation is crucial to optimize immune-checkpoint inhibitors in gastric cancer treatment.

Indexed as

Antineoplastic Agents, ImmunologicalStomach NeoplasmsAgedBiomarkersHumansMaleNeoplasm Recurrence, LocalNivolumabReceptors, Antigen, T-CellAntineoplastic Agents, ImmunologicalBiomarkersNivolumabReceptors, Antigen, T-Cellgastric cancerimmune responsenivolumabRNA-Seqtumor microenvironment

Identifiers

PMID38068925
PMCPMC10706573
OpenAlexW4388906704

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.