Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.

PD-1 is a key negative regulator of CD8 T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects.

Hyperactive Dendritc Cells Redirect Aged Antitumor Immunity.

Aging is one of the biggest risk factors for cancer development. More than 85% of all cancers occur in individuals above 55 years old, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis.

The aged tumor microenvironment limits T cell control of cancer.

The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8 T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8 T cell infiltration and function.