Evidence map›Paper›PMID 41372921›Full record

ArticleMolecular cancer2025

Immune cell senescence drives responsiveness to immunotherapy in melanoma.

Pavlos Pantelis, Dimitrios Christos Tremoulis, Konstantinos Evangelou, Panagiotis Bakouros, Sophia Magkouta, Orestis A Ntintas, Dimitris Veroutis, Giorgos Theocharous, Ioannis V Kostopoulos, Dimitris-Foivos Thanos and 19 more

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In one paragraph

Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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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

29 authors.

Pavlos Pantelis *Department of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Dimitrios Christos Tremoulis *Department of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Konstantinos Evangelou *Department of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Panagiotis BakourosDepartment of Biology, Flow Cytometry Unit, National and Kapodistrian University of Athens, Athens, 15701, Greece.
Sophia MagkoutaDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Orestis A NtintasDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Dimitris VeroutisDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Giorgos TheocharousDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Ioannis V KostopoulosDepartment of Biology, Flow Cytometry Unit, National and Kapodistrian University of Athens, Athens, 15701, Greece.
Dimitris-Foivos ThanosDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Eftychia ChatziioannouDepartment of Dermatology, Division of Dermatooncology, University of Tuebingen, Tuebingen, 7207, Germany.
Ioanna A AnastasiouDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Nefeli LagopatiLaboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Dimitrios ValakosBiomedical Research Foundation, Academy of Athens, Athens, 11527, Greece.
Dimitrios SkaltsasIntelligencia Inc, New York, NY, 10014, USA.
Oltin Tiberiu PopInstitute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, CH-9007, Switzerland.
Marie Therese AbdouInstitute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, CH-9007, Switzerland.
Sarantis GagosBiomedical Research Foundation, Academy of Athens, Athens, 11527, Greece.
Dimitris KletsasLaboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, 15341, Greece.
Dimitris ThanosBiomedical Research Foundation, Academy of Athens, Athens, 11527, Greece.
Alexandros J StratigosFirst Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, 161 21, Greece.
Martin RöckenDepartment of Dermatology, Division of Dermatooncology, University of Tuebingen, Tuebingen, 7207, Germany.
Lukas FlatzDepartment of Dermatology, Division of Dermatooncology, University of Tuebingen, Tuebingen, 7207, Germany.
George P ChrousosUniversity Research Institute of Maternal and Child Health and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Dimitrios VlachakisUniversity Research Institute of Maternal and Child Health and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Ourania E TsitsilonisDepartment of Biology, Flow Cytometry Unit, National and Kapodistrian University of Athens, Athens, 15701, Greece.
Russell PettyDivision of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD19SY, UK.
Timokratis KaramitrosBioinformatics and Applied Genomics Unit, Hellenic Pasteur institute, Athens, 11521, Greece.
Vassilis G GorgoulisDepartment of Histology and Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. VGorgoulis001@dundee.ac.uk.

Funding

General Secretariat for Research and Technology 2020ΣЕ01300001Hellenic Foundation for Research and Innovation 20554Hellenic Foundation for Research and Innovation 3782, 2906Nicholas and Sofula Kotopoulos Trust donationNKUA-SARG 70/3/8916
6 · The paper itself

Abstract

backgroundImmunotherapy has significantly improved cancer treatment. However, it is not effective in all cancer patients, rendering the need to further delineate the differences among responders and non-responders at the molecular and cellular level. Unresponsiveness to immunotherapy has been attributed to dysfunctional immune cell states such as T-cell exhaustion and anergy, whereas the contribution of cellular senescence remains elusive. Herein, we have investigated the role of immune cell senescence in the response to checkpoint inhibitors in melanomas where these immunotherapies are applied as a first line treatment.

methodsTwo senescence detecting complementary approaches were utilized in a case control study we conducted. First, we implemented a senescence molecular signature we developed, termed "SeneVick", retrospectively in a single cell RNA-seq dataset from melanoma patients who received immunotherapy. Prior to this analysis, the signature was extensively validated in a variety of cell/tissue contexts, senescence types and species. Second, cellular senescence was assessed via an established experimental algorithmic approach in circulating immune cells of an analogous melanoma clinical cohort.

resultsMelanoma patients who did not respond to immunotherapy exhibited increased cellular senescence in the CD8 + T-cell, CD4 + T-cell, B-cell (CD19 + /CD20 +) and NK cell compartments compared to responders. This phenomenon was independent of patients' clinical features (age, sex, melanoma type, stage) and not an outcome of immunotherapy, in contrast to conventional anti-cancer treatments. Interestingly, alterations of cell-to-cell interactions among the immune sub-populations in non-responders compared to responders were identified, supporting, along with cytotoxicity assays, that senescent immune cells display immunosuppressive properties driving defective immune responses and treatment failure.

conclusionOverall, our findings provide evidence that cellular senescence within the immune cell compartment of the tumor micro-environment is a potent determinant of the response to immunotherapy and pave the way for strategies targeting it as promising approaches to improve the outcome of such interventions.

Indexed as

Cellular SenescenceImmunotherapyMelanomaCase-Control StudiesFemaleHumansImmune Checkpoint InhibitorsMaleRetrospective StudiesImmune Checkpoint InhibitorsGLF16Immune cell senescenceImmunotherapyMelanomaNon-respondersRespondersSeneVickSenoprobe

Identifiers

PMID41372921
PMCPMC12717699

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.