Evidence map›Paper›PMID 40909828›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.

Samuel J Wright, Sarah Kang, Minae An, You Jeong Heo, Milan Parikh, Lynn Bi, Hyuk Lee, Graydon Moorehead, Nicholas Haradhvala, Sung Hee Lim and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Samuel J WrightThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sarah KangThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Minae AnExperimental Therapeutics Development Center, Samsung Medical Center, Seoul, Korea.
You Jeong HeoNeocella, Inc. Irvine, CA, USA.
Milan ParikhThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lynn BiThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hyuk LeeDepartment of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Graydon MooreheadThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas HaradhvalaThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sung Hee LimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seung Tae KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Gad GetzThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nir HacohenThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jeeyun LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Arnav MehtaThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samuel J KlempnerThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-4062-0808
Ryan J ParkThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Funding

Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
NCI NIH HHS K12 CA087723
6 · The paper itself

Abstract

The addition of aPD1 to 5-FU/platinum in advanced gastric cancer (GC) yields variable responses. To understand cooperativity between chemotherapy and immunotherapy, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA- and TCR-sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients. We observed greater abundance, persistence, and recruitment of T cells with predicted tumor-reactivity in patients with prolonged progression-free survival (slow progressors). Increased B cell abundance and predicted B cell to T cell interactions supported T cell memory and co-stimulation, providing a mechanism for increased abundance and persistence of progenitor-exhausted and tumor-reactive T cells in slow progressors. T cell clones emerging in the tumor after immunotherapy were in the blood before treatment only in slow progressors. Our study thus highlights pre-treatment and early chemotherapy-induced T cell dynamics and B cell to T cell interactions that may drive durable response to chemoimmunotherapy in GC.

Identifiers

PMID40909828
PMCPMC12407690

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Registered trials

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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.