Evidence map›Paper›PMID 40227595›Full record

ReviewCancers2025

Unveiling Extramedullary Myeloma Immune Microenvironment: A Systematic Review.

Kassiani Boulogeorgou, Maria Papaioannou, Sofia Chatzileontiadou, Elisavet Georgiou, Amalia Fola, Sofia-Eleni Tzorakoleftheraki, Evdoxia Hatjiharissi, Triantafyllia Koletsa

Abstract readReview
In one paragraph

Review in Cancers, 2025. 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
–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

4 citing papers in PubMed.

  1. Article
  2. Extramedullary Disease-Achilles Heel in Myeloma?American journal of hematology · 2026
    Review
  3. Review
  4. Review
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

8 authors.

Kassiani BoulogeorgouDepartment of Pathology, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.ORCID 0000-0001-7625-1680
Maria PapaioannouHematology Unit, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Sofia ChatzileontiadouHematology Unit, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Elisavet GeorgiouDepartment of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.ORCID 0000-0001-8732-0610
Amalia FolaHematology Unit, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.ORCID 0009-0002-0300-7171
Sofia-Eleni TzorakoleftherakiDepartment of Pathology, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
Evdoxia HatjiharissiHematology Unit, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.ORCID 0000-0002-8233-0542
Triantafyllia KoletsaDepartment of Pathology, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.ORCID 0000-0002-4435-3532

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesIn recent years, efforts by the scientific community to elucidate the underlying mechanisms of clonal expansion and selection within tumors have led to the theory of "tumor ecosystems", implicating, among other factors, the role of the microenvironment in therapy resistance and tumor progression. In this context, the contribution of the microenvironment in the development of multiple myeloma (MM) is being investigated, imparting great emphasis on continuous clonal evolution. This process gives rise to aggressive clones with the potential to spread to extramedullary sites, rendering any treatment strategy practically ineffective. This systematic review aimed to gather knowledge about the immune microenvironment (IME) of extramedullary plasma cell myeloma and the differences in immune synthesis between medullary and extramedullary disease (EMD).

methodsA search strategy according to PRISMA guidelines was conducted in seven databases, and six articles meeting the inclusion criteria were encompassed in the study.

resultsResults obtained from molecular analysis as well as flow cytometry and immunofluorescence indicated profound genetic instability at EMD sites along with spatial and temporal heterogeneity of the IME, implying a possible correlation between them. Both genetic and microenvironment variability were notably greater in EMD compared to medullary disease. The establishment of an immunosuppressive microenvironment was the rule, with exhausted CD8+ and natural killer (NK) cells, M2 macrophages, and inactivated dendritic cells found co-localized with neoplastic plasma cells, whereas cytotoxic CD8+ cells, M1 macrophages, and active dendritic cells congregated in tumor-free areas. Post-therapy alterations in the immune milieu were also noted and were concerned mostly the percentages of Tregs and MDSCs.

conclusionsThe recognition of the microenvironment-myeloma cell interplay is essential for designing specific therapeutic strategies and ameliorating disease prognosis.

Indexed as

extramedullary multiple myelomaimmune exhaustionmicroenvironmentmicroenvironment heterogeneityplasma cell neoplasm

Identifiers

PMID40227595
PMCPMC11987838

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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.