General Information

New B7 Family Immune Checkpoint Proteins

Recently 5 new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6 & B7-H7, were identified, all of them possibly of high interest in immunotherapy research.

HVEM – BTLA – LIGHT – CD160 Network

The checkpoint receptors/ligands system HVEM, LIGHT, CD160 and BTLA (CD272) is part of a complex network of overlapping receptor interactions.

TIGIT – CD155 – CD112 – CD226 Network

Tumour cells exploit the dominance of the inhibitory TIGIT pathway to avoid immune-mediated destruction.

LAG-3 – Major Histocompatibility Complex (MHC) – T Cell Receptor (TCR) Pathway

Dual inhibition of LAG-3 and other checkpoint pathways may synergistically increase T cell antitumour activity.

CTLA-4 [CD152] – CD80 – CD86 – CD28 Network

Targeting CTLA-4 restores immune response by more accumulation, function & survival of T cells, depletion of Tregs & better antitumour response.

CD40 – CD40L Pathway

CD40 is a member of the TNF receptor family expressed by APCs and B cells whereas its ligand, CD40L (CD154), is expressed by activated T cells.

GITR – GITRL Pathway

Glucocorticoid-induced TNFR-related protein is an activating receptor on the surface of T cells and other immune cells, binding to its ligand GITRL.

CD137 – CD137L Pathway

CD137 is an activating receptor binding to CD137L, expressed on natural killer (NK) cells & T cells, therefore triggering innate & adaptive immunity.

TIM-3 – Galectin-9 Pathway

T cell immunoglobulin & mucin-3 (TIM-3; HAVcr-2) is an immune checkpoint receptor involved in the suppression of both innate & adaptive immune cells.

ICOS [CD278] – ICOSL [CD275] Pathway

ICOS/ICOSL signalling leads to the activation, proliferation and survival of cytotoxic T cells, as well as the survival of memory T cells.