PhD Scientific Days 2026

Poster Session 1.A - Molecular Medicine

Overcoming antigen presentation deficiency and resistance to immune based therapies in melanoma

Előadó neve

Lakatos, Alexandra

Neptune code

Q6A6I1

Előadó munkahelye

Semmelweis University, Faculty of Medicine, Department of Physiology

Előadó telefonszáma

+36305514464

Előadó e-mail címe

lakatos.alexandra@phd.semmelweis.hu

Az előadás címe

Overcoming antigen presentation deficiency and resistance to immune based therapies in melanoma

Szerző(k) neve és munkahelye

Alexandra I.T. Lakatos¹, Dorottya M.P. Pál¹, Botond L. Szabolcs^1,2, Katalin Buday¹, David E. Fisher³, Lajos V. Kemény^1,2,3

1: HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, 37-47. Tűzoltó street 1094 Budapest, Hungary
2: Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, 41. Mária street 1085 Budapest, Hungary
3: Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

Bemutatás módja

Poszter

Szekció

Poster Session 1.A - Molecular Medicine

Language of the presentation

Hungarian

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction: Immune checkpoint blockade (ICB) has significantly improved melanoma therapy; however, resistance remains a major challenge. A common mechanism is the loss of antigen presentation, which disrupts CD8⁺ T cell–mediated tumor recognition. This underscores the need to identify alternative immune pathways capable of targeting tumor cells independently of MHC class I.
Aims: We hypothesize that, in the absence of MHC-I expression, an alternative T cell-independent mechanism can be leveraged for melanoma treatment. We aim to identify novel therapeutic strategies to overcome resistance mechanisms associated with impaired antigen presentation.
Methods: We developed an in vivo melanoma model deficient in β2-microglobulin (B2M), a key component of the MHC-I complex. Using this model, we performed a pooled in vivo CRISPR-Cas9 screen targeting ~600 epigenetic regulators in immunocompetent and immunodeficient mice. Candidate genes were prioritized based on guide RNA depletion and bioinformatic analysis. Selected genes were further investigated by generating single-cell knockout clones, followed by validation at the DNA, RNA, and protein levels. Subsequent in vivo experiments have been initiated to evaluate the impact of candidate gene loss on tumor growth and immune control.
Results: Tumor growth patterns differed between immunocompetent and immunodeficient mice, indicating anti-tumor responses independent of CD8⁺ T cells. The screen identified ~20 genes with significantly depleted guide RNAs in tumors from immunocompetent mice, suggesting roles in immune evasion under MHC-I–deficient conditions. Four top candidates were selected for further validation, which is currently ongoing.
Conclusion: Our model enables investigation of MHC-I–independent tumor immunity. The identified genes may represent regulators of T cell–independent tumor clearance and potential targets to improve ICB efficacy in resistant melanoma.
Funding: This work was supported by the Hungarian National Research, Development and Innovation Office (OTKA FK138696), the EU Horizon 2020 program (739593), and the Lendület “Momentum” Program of the Hungarian Academy of Sciences (LP2024-12/2024).

University

Semmelweis University

Supervisor

Lajos Vince Kemény MD, PhD

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 after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7350

Start

17:42

End

17:45