Table 1.

Immune regulatory pathways linked to tumor tolerance

Pathway	Description
cell types:
MDSCs	tumor infiltrating & circulating monocytic regulatory cells
DCs	specialized subsets suppress effector T cells & activate Tregs
MΦs	Specialized subsets are tumor infiltrating regulatory cells
Tregs	potent regulatory CD4 T cells (auto/tumor antigen-specific)
NK cells	non-antigen specific regulatory lymphocytes
Mast cells	innate immune cells active in wound healing, host defense & allergy
molecules:
CTLA4	induces T cell anergy & induces IDO in DCs (blocked by Ipilimumab)
PD-1(PD-L)	inhibitory co-stimulator pathway in T cells & Tregs
GITR	mediates immune regulation to steroids
TGFβ, IL-10	regulatory cytokines
metabolic pathways:
IFNs (I, II)	immune activating cytokines that can stimulate or suppress immunity
IDO1 (IDO2?)	catabolizes Trp to suppress effector T cells & activate Tregs
TDO	as for IDO
TPH-1	consumes Trp to promote tolerance
ARG (I, II)	catabolizes Arg to suppress effector T cells and induce Tregs
mTOR	senses amino acid availability (nutrient check point control)
GCN2 kinase	amino acid depletion sensor (via tRNA); induces cell stress responses
AhR	senses Kyn (and other Trp catabolites) to regulate immunity