OUR SCIENCE
The role of Antigen Presentation in Tumor Immune Rejection
The adaptive immune system is the body’s most powerful defense against cancer, with T cells capable of recognizing and eliminating malignant cells with remarkable specificity. Checkpoint inhibitors and adoptive cell therapies boost T cell activity, but without effective and persistent cancer antigen presentation inside tumors, these strategies often fall short, leading to resistance and relapse. Our studies have demonstrated that antigen presentation within the tumor microenvironment is a decisive driver of T cell-mediated rejection, positioning antigen-presenting cell–T cell crosstalk as a powerful but underexploited therapeutic axis. By restoring and enhancing this interface, we unlock new opportunities for durable cancer therapies.
Approach
OncoGenesys integrates deep biological insight with state-of-the-art technology to follow a clear, three-stage innovation pipeline:
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Target Discovery
Using in vivo and in vitro models of tumor-immune interactions, we identify novel therapeutic targets with a focus on professional and atypical antigen-presenting cells. We combine this with AI-driven analysis of single-cell and spatial omics datasets to pinpoint biomarkers and immune vulnerabilities across cancer types. -
Drug Development
Our team of chemists and bioinformaticians uses cheminformatics, structure-based design, and medicinal chemistry to develop small molecules and biologics that modulate key immune pathways. -
Preclinical Testing
We validate candidate drugs through robust preclinical assays, including functional immune co-cultures, tumor slice culture and in vivo models, to evaluate efficacy, specificity, and translational potential.
Our Vision
Current immunotherapies largely fail at the critical interface between T cells and antigen-presenting cells, where the anti-tumor immune response is initiated and maintained. By restoring the critical dialogue between T cells and antigen-presenting cells, we aim to transform the treatment landscape for patients with immunotherapy-resistant cancers. Our innovative approach harnesses the power of adaptive immunity at the tumor site to unlock durable, life-saving responses.
Key Publications
Tsoumakidou M. The advent of immune stimulating CAFs in cancer. Nat Rev Cancer. 2023; 23:258–269
Kerdidani D, Chouvardas P, Arjo AR, Giopanou I, Ntaliarda G, Guo YA, Tsikitis M, Kazamias G, Potaris K, Stathopoulos GT, Zakynthinos S, Kalomenidis I, Soumelis V, Kollias G, Tsoumakidou M. Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma. Nat Commun. 2019;10(1):1405.
Aerakis E, Chatzigeorgiou A, Alvanou M, Matthaiakaki-Panagiotaki M, Angelidis I, Koumadorakis D, Galaras A, Hatzis P, Kerdidani D, Makridakis M, Vlachou A, Malissen B, Henri S, Merad M, Tsoumakidou M. Interferon-induced lysosomal membrane permeabilization and death cause cDC1-deserts in tumors. doi: https://doi.org/10.1101/2022.03.14.484263; BioRxiv.
Kerdidani D, Magkouta S, Chouvardas P, Karavana V, Glynos K, Roumelioti F, Zakynthinos S, Wauters E, Janssens W, Lambrechts D, Kollias G, Tsoumakidou M. Cigarette Smoke-Induced Emphysema Exhausts Early Cytotoxic CD8+ T Cell Responses against Nascent Lung Cancer Cells. J Immunol. 2018;201(5):1558-1569.
Kerdidani D, Aerakis E, Verrou K.M, Angelidis I, Douka K, Maniou M.A, Stamoulis P, Goudevenou K, Prados A, Tzaferis C, Ntafis V, Vamvakaris I, Kaniaris E, Vachlas K, Sepsas E, Koutsopoulos A, Potaris K, Tsoumakidou M. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J Exp Med. 2022; 219 (2): e20210815.