Evidence map›Paper›PMID 41184524›Full record

ArticleAnnals of hematology2025

Proinflammatory bone marrow niches and neutrophil activation are associated with TIGIT expression in multiple myeloma.

Valeria Tomarchio, Francesca Arciprete, Monica Di Cecca, Giulia Maricchiolo, Viola Velardi, Mariantonietta Tafuri, Antonella Bianchi, Vittoria Morano, Barbara Mecorio, Luigi Rigacci and 3 more

Abstract read
In one paragraph

Article in Annals of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Valeria Tomarchio *Hematology, stem cell transplantation, Fondazione Policlinico Universitario Campus Bio medico, Rome, Italy.
Francesca Arciprete *Laboratory of Microscopic and Ultrastructural Anatomy Campus Bio- Medico, University of Rome, Rome, Italy.
Monica Di CeccaHematology, stem cell transplantation, Fondazione Policlinico Universitario Campus Bio medico, Rome, Italy.
Giulia MaricchioloDept of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Viola VelardiLaboratory of Microscopic and Ultrastructural Anatomy Campus Bio- Medico, University of Rome, Rome, Italy.
Mariantonietta TafuriHematology, stem cell transplantation, Fondazione Policlinico Universitario Campus Bio medico, Rome, Italy.
Antonella BianchiUnit of Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico Rome, Rome, Italy.
Vittoria MoranoDept of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Barbara MecorioHematology, University Campus Bio medico, Rome, Italy.
Luigi RigacciHematology, stem cell transplantation, Fondazione Policlinico Universitario Campus Bio medico, Rome, Italy.
Anna Crescenzi *Dept of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
Maria Zingariello *Laboratory of Microscopic and Ultrastructural Anatomy Campus Bio- Medico, University of Rome, Rome, Italy.
Ombretta Annibali *Hematology, stem cell transplantation, Fondazione Policlinico Universitario Campus Bio medico, Rome, Italy. O.annibali@policlinicocampus.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple Myeloma (MM) is the second most frequent hematologic malignancy in adults in the Western world. The bone marrow microenvironment plays a critical role in MM progression by supporting malignant plasma cell (PC) survival, immune evasion, and proliferation. Among immune checkpoints, TIGIT has recently emerged as a relevant immunoregulatory molecule, capable of dampening cytotoxic responses and enhancing immune suppression. We investigated the expression of TIGIT in the bone marrow of newly diagnosed MM patients and its correlation with disease characteristics and microenvironmental features. We enrolled 25 consecutive patients with newly diagnosed MM. Bone marrow samples were collected for cytomorphology, cytogenetics (FISH), and immunohistochemistry using the Cytomatrix system. TIGIT expression was analyzed in bone marrow-infiltrating immune cells. Histological evaluation and confocal microscopy assessed immune cell localization, neutrophil extracellular trap (NET) formation, and proinflammatory cytokine expression. Clinical parameters, staging (ISS, R-ISS, R2-ISS), cytogenetic risk, and laboratory values were correlated with TIGIT status. TIGIT was expressed in 86% (19/22) of evaluable samples. TIGIT-positive patients had a significantly higher frequency of advanced R-ISS stages (p = 0.01), high-risk cytogenetics (100%), and elevated LDH (> 220 mU/ml, 100% TIGIT+). Among patients with PC% >60% or FLC ratio > 100, 92% were TIGIT+. Morphological differences were evident between groups: TIGIT-negative PCs were larger and altered, while TIGIT-positive PCs showed polarized nuclei and proximity to neutrophils. TIGIT-positive samples displayed increased neutrophils undergoing NETosis, as confirmed by neutrophil elastase and Ly6b co-expression (p = 0.0067). Elevated IL-6 (p = 0.0003) and IL-8 (p = 0.004) in TIGIT-positive samples suggest a proinflammatory microenvironment promoting neutrophil recruitment and NETosis. TIGIT expression in the bone marrow of MM patients is associated with more aggressive disease features and an inflammatory microenvironment enriched with NET-forming neutrophils. These findings support TIGIT as a potential biomarker of disease severity and a therapeutic target in MM.

Indexed as

Bone MarrowGene Expression Regulation, NeoplasticMultiple MyelomaNeoplasm ProteinsNeutrophil ActivationReceptors, ImmunologicAdultAgedAged, 80 and overFemaleHumansInflammationMaleMiddle AgedNeutrophilsTumor MicroenvironmentNeoplasm ProteinsReceptors, ImmunologicTIGIT protein, humanIL-8Ly6bMMNETTIGIT

Identifiers

PMID41184524
PMCPMC12672760

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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.