Fig. 2

Immune-metabolism in the tumor microenvironment (TME). Fast growing tumor cells, under hypoxic conditions, lead to upregulation of HIF-1α, enhanced consumption of nutrients, increased glycolysis and increased production of adenosine and lactate, all of which in turn produce a microenvironment rich in adenosine, lactate and HIF-1α, but with a scarcity of nutrients for tumor-infiltrating immune cells. This metabolic microenvironment programs the immune cells such that (1) anergic T cells, with inefficient proliferation and effector function, as well as (2) regulatory T cells, are predominant in TME. Furthermore, T cells with increased expression of a number of immune checkpoints and loss of effector functions, a hallmark or exhausted T cells, are characteristics of TME. This figure depicts T cells as an example immune cell type for clarity, but as described in the manuscript text, other lymphoid and myeloid cells are also present in the TME and are intensively involved in tumor progression