We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The "folding GO" acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a "One but All" modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.