PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

METFORMIN'S IMPACT ON T-CELL IMMUNOSENESCENCE IN MELANOMA PATIENTS UNDERGOING IMMUNOCHECKPOINT INHIBITOR TREATMENT

Előadó neve

Dr. Varga Viktória

Neptun code

S7RJXB

Előadó munkahelye

SE Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

06706362241

Előadó e-mail címe

vivarga@gmail.com

Az előadás címe

METFORMIN'S IMPACT ON T-CELL IMMUNOSENESCENCE IN MELANOMA PATIENTS UNDERGOING IMMUNOCHECKPOINT INHIBITOR TREATMENT

Szerző(k) neve és munkahelye

Viktória Varga¹, Dorottya Moldvai¹, Fatime Szalai¹, Ildikó Krencz¹, Dániel Sztankovics¹, Ágnes Márk¹, Gábor Barna¹, Daniella Kuzmanovszki², Beáta Kun², Péter Holló², Anna Sebestyén¹

1: SE Department of Pathology and Experimental Cancer Research
2: Semmelweis University, Department of Dermatology, Venereology and Dermatooncology

Bemutatás módja

Poszter

Szekció

Poster Session II. - E: Pathological and Oncological Sciences

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Dysfunctional T cells, including exhausted (T-ex: PD-1+, TIM3+, LAG3+) and senescent (T-sen: CD27-CD28-CD57+CD45RA-) populations, can affect the antitumor immune responses and the efficacy of immune checkpoint inhibitor (ICI) therapy. While ICI treatment can reverse T-cell exhaustion, it does not reactivate senescent T cells. Metformin, anti-diabetic drug can modulate immunosenescence with improving the efficacy of ICI therapy. This preclinical observation needs additional studies, because the clinical evidences remain inconclusive.
Our aims is to characterize phenotype and changes in proportion of exhausted/senescent T cells in blood samples of advanced melanoma (AM) patients receiving ICIs comparing diabetic patients treated with metformin (n=10, Gr1) to age-gender-matched non-diabetic patients (n=10, Gr2).
In our prospective study, multicolor flow cytometry (marker panel - CD3, CD4, CD8, KLRG, CD57, CD28, CD36, PD1, CD56, CD16) are used to characterize immune cells from fresh peripheral blood samples of MM patients.
Based on our results, the percentage of peripheral T-ex and T-sen cells in AM patients (Gr1: T-sen: 3.43-27.75%, mean: 12.11%, T-ex: 11.6-50.58%, mean: 29.62%, Gr2: T-sen: 2.52-42%, mean: 18.08%, T-ex: 9.3-57.5%, mean: 29.38%) showed significant individual differences in both groups. Patients receiving metformin have lower proportion of T-sen cells (Gr1: 12.11% vs. Gr2: 18.08%), while the number of T-ex cells does not show any significant differences. In this small cohort the percentage of T-ex cells decreased (Gr1: T-ex 31.3 vs. 8.4%, Gr2: T-ex: 26.07% vs 12.74%) and the percentage of senescent T cells increased (Gr1: T-sen 12.11% vs. 18.72%, Gr2.: T-sen: 13% vs 18.74%) after ICI treatment. The evaluation of clinical responses is currently ongoing.
Based on our results metformin could have senolytic effect, lowering the number of T-sen cells in metformin using patients, while ICI influence both exhaustion and senescence in peripheral T cells of all studied MM patients. Our further studies with expanded sample size and additional in situ immune-pathologic analyses of tissue samples may help to understand the role of these alterations and contribute to find new biomarkers for personalized MM treatments.
FUNDING: 2024-2.1.1-EKÖP-2024-00004, SEMMELWEIS 250+, EFOP-3.6.3-VEKOP-16-2017-00009, TKP2021-EGA-24 [S.A.], NKFI-K-142799 [S.A.]

University

Semmelweis University

Supervisor

Prof. Dr. Anna Sebestyén

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8000

Start

18:18

End

18:24