2018 Nobel Prize in physiology or medicine

Abstract

Figure 1

Antibodies that block CTLA‐4 or PD‐1/PD‐L1 can induce antitumor responses. (left), Following the initial activation of a tumor‐specific T cell in the lymph node with antigen‐presenting cells (APC) through the interaction of the T‐cell receptor (TCR) with MHC presented tumor‐derived peptide, CTLA‐4 is upregulated and acts as a negative regulator of costimulation, which can be blocked with anti‐CTLA‐4 antibodies. Blockade of CTLA‐4 on regulatory T cells (Tregs) also relieves their suppression of T‐cell activation or effector function. (Right), Activated T cells circulate throughout the blood and traffic into tumors where they can be activated upon recognition of cognate antigen presented by cancer or immune cells. This activation leads to upregulation of PD1 and production of IFN‐γ, which can upregulate PD‐L1 on both tumor and immune cells in the tumor microenvironment. This mechanism, termed adaptive immune resistance, can suppress effector function of tumor‐specific T cells, which can be re‐invigorated using antibodies that block PD1 or PD‐L1.