Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kaptein, P; Slingerland, N; Metoikidou, C; Prinz, F; Brokamp, S; Machuca-Ostos, M; de, Roo, G; Schumacher, TNM; Yeung, YA; Moynihan, KD; Djuretic, IM; Thommen, DS.
CD8-targeted IL2 unleashes tumor-specific immunity in human cancer tissue by reviving the dysfunctional T cell pool.
Cancer Discov. 2024;
Doi: 10.1158/2159-8290.CD-23-1263
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- Co-authors Med Uni Graz
- Prinz Felix
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- Abstract:
- Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune checkpoint blockade can restore antitumor T cell function in some patients, however most do not respond to this therapy, often despite T cell infiltration in their tumors. We here explored a CD8-targeted IL2 fusion molecule (CD8-IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8-IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8-IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8-IL2 was able to functionally reinvigorate T cells in tumors resistant to anti-PD-1, underscoring its potential as a novel treatment strategy for cancer patients.