Hypoxia is a common feature of tumour microenvironment (TME), leading to T cell exhaustion. Exhaustion is a differentiation state where T cells show a reduction in their antitumor activity. Therefore, it represents a limitation in current cancer immunotherapies. In order to further understand the mechanism involved in the terminal differentiation of CD8+ T cells under hypoxic conditions, we performed a proteomic analysis of CD8+ T cells subjected to hypoxia (1% O2).