Evidence map›Paper›PMID 41346287›Full record

ArticleBlood advances2026

Proinflammatory GSDMD activation in live macrophages and DLBCL cells marks cognate interactions and better prognosis.

Xue Kong, Zijun Y Xu-Monette, Zhenming Xu, Eric D Hsi, Xiaoxian Zhao, Hui Yan, Harry Nunns, Kelly Au, Carlo Visco, Alexandar Tzankov and 21 more

Abstract read
In one paragraph

Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

31 authors.

Xue KongHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.
Zijun Y Xu-MonetteHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.ORCID 0000-0002-7615-3949
Zhenming XuDepartment of Microbiology, Immunology and Molecular Genetics, Joe R. and Teresa Lozano Long School of Medicine, The University of Texas at San Antonio, San Antonio, TX.ORCID 0000-0002-5822-0570
Eric D HsiDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Xiaoxian ZhaoDepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC.
Hui YanDepartment of Microbiology, Immunology and Molecular Genetics, Joe R. and Teresa Lozano Long School of Medicine, The University of Texas at San Antonio, San Antonio, TX.
Harry NunnsNeoGenomics Laboratories, Aliso Viejo, CA.
Kelly AuHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.
Carlo ViscoDepartment of Engineering for Innovative Medicine, University of Verona, Verona, Italy.ORCID 0000-0003-2863-0883
Alexandar TzankovDepartment of Histopathology and Autopsy, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Karen DybkaerDepartment of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.ORCID 0000-0003-2488-435X
Shuna YaoHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.
Dehong WuHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.
Chang WangHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.ORCID 0000-0001-7999-9627
Alexander M XuDivision of Hematology and Cellular Therapy, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0003-4877-4358
Zenggang PanDepartment of Pathology, University of Colorado School of Medicine, Aurora, CO.ORCID 0000-0003-4537-3356
Benjamin M ParsonsDepartment of Medical Oncology, Gundersen Health System, La Crosse, WI.ORCID 0000-0002-5634-2937
April ChiuDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.ORCID 0000-0002-6431-2666
Wayne TamDepartment of Pathology, Northwell Health, New York, NY.
Santiago Montes-MorenoTranslational Hematopathology Laboratory and Anatomic Pathology Service, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Fenghuang ZhanMyeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR.ORCID 0000-0001-5417-2973
Leon Bernal-MizrachiDepartment of Cancer Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
Youli ZuDepartment of Pathology, Houston Methodist Hospital, Houston, TX.
Shanxiang ZhangDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE.
Michael B MøllerDepartment of Pathology, Odense University Hospital, Odense, Denmark.ORCID 0000-0003-2041-3630
Weina ChenDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.ORCID 0000-0001-5638-4371
Qingyan AuNeoGenomics Laboratories, Aliso Viejo, CA.
Akil MerchantDivision of Hematology and Cellular Therapy, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0001-7472-822X
Govind BhagatDepartment of Pathology, Saint Louis University School of Medicine, SSM Health, Saint Louis, MO.ORCID 0000-0001-6250-048X
Yong LiDepartment of Medicine, Baylor College of Medicine, Houston, TX.ORCID 0000-0001-8838-1714
Ken H YoungHematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC.ORCID 0000-0002-5755-8932

Funding

Tissue ResourceP50CA126752 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, HELEN E HESLOP · 2007 to 2026
$51.4M
NCI NIH HHS P50 CA126752
6 · The paper itself

Abstract

abstractPyroptosis is a form of programmed cell death characterized by the cleavage of the gasdermin (GSDM) family proteins that form pores in the plasma membrane, cell rupture, and the release of proinflammatory cytokines. In this study, we performed immunohistochemistry for cleaved gasdermin D (GSDMD), gasdermin E (GSDME) N-terminus, and gasdermin C (GSDMC) in 2 different cohorts of diffuse large B-cell lymphoma (DLBCL) and analyzed the impact of GSDM expression on prognosis and immunity. The results showed frequent cleaved GSDMD (N-terminal) expression. Only cytoplasmic GSDMD N-terminal expression correlated with significantly better patient survival in the 2 cohorts. In contrast, GSDME was mainly expressed in the vascular endothelium, and correlated with significantly adverse prognostic effect. Correlating with the multiplex fluorescent immunohistochemistry results, we found that cytoplasmic GSDMD N-terminal expression was associated with increased CD38+ (activated) M1 macrophages in both cohorts, cognate interactions between live DLBCL cells and activated M1 macrophages (and T cells), and lower PD-1/PD-L1 expression in the analyzed cases. In contrast, T-cell pyroptosis, lymphoma cell-resistance to cell death, and phagocytosis by M2 macrophages were observed in tissues with predominantly nuclear GSDMD N-terminal expression. Bulk gene expression profiling and deconvolution analysis revealed associations of cytoplasmic GSDMD N-terminal expression with downregulation of "Don't eat me"-signaling genes, upregulation of many RNA genes, decreased frequency of "inflammatory" lymphoma microenvironment subtype, increased frequencies of prognostically favorable cell states and ecotypes, and decreased frequency of T-cell exhaustion state. In summary, this study showed distinct cellular and subcellular patterns of 3 GSDM proteins and their associated immune response phenotypes and prognostic effects, with implications for novel therapeutic strategies for B-cell lymphoma.

Indexed as

Intracellular Signaling Peptides and ProteinsLymphoma, Large B-Cell, DiffuseMacrophagesNeoplasm ProteinsPhosphate-Binding ProteinsFemaleGasderminsHumansMalePrognosisPyroptosisGasderminsGSDMD protein, humanIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsPhosphate-Binding Proteins

Identifiers

PMID41346287
PMCPMC12969404

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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.