Evidence map›Paper›PMID 41340154›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Circulating CD137⁺Treg cells and LOX-1⁺PMN-MDSCs as biomarkers of immunotherapy resistance in (R/M) HNSCC patients.

Angela Asquino, Alessio Cirillo, Lidia Strigari, Angelica Pace, Chiara Napoletano, Lucrezia Tuosto, Flavio Valentino, Andrea Ballario, Daniele Santini, Marianna Nuti and 3 more

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Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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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

13 authors.

Angela AsquinoLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Alessio CirilloDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Lidia StrigariDepartment of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Angelica PaceLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Chiara NapoletanoLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Lucrezia TuostoLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Flavio ValentinoLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Andrea BallarioDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Daniele SantiniDivision of Oncology, Department of Science and Medical-Surgery Biotechnologies, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Marianna NutiLaboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Andrea BotticelliDivision of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Aurelia Rughetti *Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy.
Ilaria Grazia Zizzari *Laboratory of Tumor Immunology and Cell Therapy, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, Italy. ilaria.zizzari@uniroma1.it.ORCID http://orcid.org/0000-0001-8263-7248

Funding

Sapienza Università di Roma RG123188B4C6C54BSapienza Università di Roma RM123188C3F3E706Sapienza Università di Roma RM124191094FCF86
6 · The paper itself

Abstract

backgroundRecurrent/metastatic head and neck squamous cell carcinoma ((R/M) HNSCC) represents one of the most aggressive and immunosuppressive cancers. Despite the introduction of immune checkpoint inhibitors (ICIs), only a limited number of patients obtain long-term benefits. In (R/M) HNSCC patients, the antitumor immune response is defective, conferring resistance and promoting tumor progression. Therefore, the identification of novel biomarkers for superior clinical outcomes and easily accessible in standard clinical settings is still an unmet clinical need.

methodsBlood liquid biopsies obtained from (R/M) HNSCC patients undergoing pembrolizumab therapy (monotherapy or in combination with chemotherapy) were analyzed by flow cytometry to evaluate the levels of circulating immunosuppressive regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), at baseline and during therapy. Correlations between these immunosuppressive immune cell subsets and clinical parameters (clinical response rate, progression-free survival (PFS), overall survival (OS) and performance status (PS)) were performed.

resultsUnivariate analysis showed that before therapy, higher circulating levels of both CD137⁺Tregs and LOX-1⁺PMN-MDSCs, identified patients with significantly worse survival. Furthermore, CD137⁺Tregs resulted also positively correlated with worse PS, while high levels of LOX-1⁺PMN-MDSCs negatively affected response to pembrolizumab, with a significant increase in non-responsive patients during therapy. Interestingly, both CD137⁺Tregs as well as LOX-1⁺PMN-MDSCs exerted a higher immunosuppression on T cell proliferation than CD137

conclusionsThe levels of blood circulating LOX-1⁺PMN-MDSCs may be proposed as non-invasive biomarkers to predict clinical outcomes of (R/M) HNSCC patients developing resistance to immunotherapy, improving patient selection and suggesting novel personalized therapies.

Indexed as

Biomarkers, TumorDrug Resistance, NeoplasmHead and Neck NeoplasmsMyeloid-Derived Suppressor CellsScavenger Receptors, Class ESquamous Cell Carcinoma of Head and NeckTumor Necrosis Factor Receptor Superfamily, Member 9AdultAgedAntibodies, Monoclonal, HumanizedFemaleHumansImmunotherapyMaleMiddle AgedPrognosisAntibodies, Monoclonal, HumanizedBiomarkers, TumorScavenger Receptors, Class ETNFRSF9 protein, humanTumor Necrosis Factor Receptor Superfamily, Member 9Anti-PD-1 immunotherapyBlood liquid biopsyCD137+ Treg cellsImmune suppressionLOX-1⁺PMN-MDSCs(R/M) HNSCC

Identifiers

PMID41340154
PMCPMC12676864

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