Evidence map›Paper›PMID 38319303›Full record

Trial reportCancer discovery2024

Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.

Minae An, Arnav Mehta, Byung Hoon Min, You Jeong Heo, Samuel J Wright, Milan Parikh, Lynn Bi, Hyuk Lee, Tae Jun Kim, Song-Yi Lee and 9 more

Open access · hybridAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
18.9field-weighted citation impact, top 1% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. CXCL12 upregulates PD-L1 expression and promotes M2 polarisation of tumour-associated macrophages to confer anti-PD-1 resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. CDK4/6 Inhibitor Priming Enhances PD-1 Blockade via SellAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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

19 authors at 5 institutions in 2 countries.

Minae An *Experimental Therapeutics Development Center, Samsung Medical Center, Seoul, Korea.ORCID 0009-0007-9575-7952
Arnav Mehta *The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0002-0313-2848
Byung Hoon Min *Department of Medicine, Division of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0001-8048-361X
You Jeong Heo *Neocella, Inc. Irvine, California.ORCID 0000-0002-7966-711X
Samuel J WrightThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0009-0006-4892-5338
Milan ParikhThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0003-1336-7883
Lynn BiThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0002-8955-8208
Hyuk LeeDepartment of Medicine, Division of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0003-4271-7205
Tae Jun KimDepartment of Medicine, Division of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0001-8101-9034
Song-Yi LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0009-0009-8123-4100
Jeonghyeon MoonDepartments of Neurology and Immunology, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0002-5384-4077
Ryan J ParkThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0003-4725-2937
Matthew R StricklandDepartment of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-7845-0712
Woong-Yang ParkGeninus Inc, Seoul, Korea.ORCID 0000-0003-4234-0380
Won Ki KangDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0002-0049-8086
Kyoung-Mee KimDepartment of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0002-1162-9205
Seung Tae KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0001-7335-1846
Samuel J KlempnerDepartment of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-4062-0808
Jeeyun LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.ORCID 0000-0002-4911-6165
Samsung Medical Center · KRBroad Institute · USHarvard University · USIncell Corporation (United States) · USYale University · US

Funding

DeGregorio Family Foundation (DFF)Doris Duke Charitable Foundation (DDCF)Korea Health Industry Development Institute (KHIDI) HR20C0025Stand Up To Cancer (SU2C) SU2C-AACR-DT-30-20Sungkyunkwan University (SKKU)
6 · The paper itself

Abstract

Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab, we transcriptionally profiled 358,067 single cells to identify evolving multicellular tumor microenvironment (TME) networks. Chemotherapy induced early on-treatment multicellular hubs with tumor-reactive T-cell and M1-like macrophage interactions in slow progressors. Faster progression featured increased MUC5A and MSLN containing treatment resistance programs in tumor cells and M2-like macrophages with immunosuppressive stromal interactions. After pembrolizumab, we observed increased CD8 T-cell infiltration and development of an immunity hub involving tumor-reactive CXCL13 T-cell program and epithelial interferon-stimulated gene programs. Strategies to drive increases in antitumor immune hub formation could expand the portion of patients benefiting from anti-PD-1 approaches. SIGNIFICANCE: The benefit of 5-FU/platinum with anti-PD-1 in first-line advanced gastric cancer is limited to patient subgroups. Using a trial with sequential anti-PD-1, we show coordinated induction of multicellular TME hubs informs the ability of anti-PD-1 to potentiate T cell-driven responses. Differential TME hub development highlights features that underlie clinical outcomes. This article is featured in Selected Articles from This Issue, p. 695.

Indexed as

Stomach NeoplasmsTumor MicroenvironmentAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsFemaleFluorouracilHumansImmunotherapyMaleMiddle AgedAntibodies, Monoclonal, HumanizedFluorouracilpembrolizumab

Identifiers

PMID38319303
PMCPMC11061611
OpenAlexW4391577415

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.