Cytotoxic CD8 T lymphocytes are an essential component of adaptive immune system for the control of infections. In chronic viral infections and cancer, however, persistent antigen stimulation drives a process of exhaustion preventing proper antigen clearance. Recently developed checkpoint inhibitors can block the interaction between inhibitory receptors and their ligands and thus reinvigorate exhausted cells, enabling them to eliminate persistent infections and advanced cancers. There is increasing interest to understanding the basic mechanisms underlying the effectiveness and limitations of checkpoint immunotherapy. In my PhD, I will address role of cross-presenting cDC1 (XCR1+) dendritic cells as well as secondary lymphoid organ FRC as critical interaction partners of CD8 T cells during chronic infection and checkpoint immunotherapy.