Open AccessPD1 functions by inhibiting CD28‐mediated co‐stimulation
Author(s) -
O'Donnell Jake S,
Smyth Mark J,
Teng Michele W L
Publication year - 2017
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1038/cti.2017.15
Subject(s) - effector , cd28 , antigen , t cell receptor , biology , blockade , t cell , cancer research , monoclonal antibody , cancer immunotherapy , co stimulation , immunotherapy , immunology , antibody , receptor , immune system , genetics
IMMUNE CHECKPOINTS IN CANCER IMMUNOTHERAPY T cells chronically exposed to antigen during cancer and persisting infections tend to undergo a phenotypic switch, in which their effector functions are significantly diminished, allowing disease to progress. These exhausted or dysfunctional T cells are unable to provide optimal control of persisting tumours and pathogens, due in part to sustained expression of co-inhibitory receptors including Programmed Death 1 (PD1).1 By blocking the interaction of PD1 with its ligands, programmed death ligands 1 and 2 (PDL1 and PDL2) expressed on either tumour cells or on antigen presenting cells (APCs), the effector functions of exhausted T cells can be, at least partially reinvigorated to provide protective immunity.2 Within the clinic, therapeutic monoclonal antibodies targeting the PD1/PDL1 pathway have proven highly effective and consistent reports of durable responses have been reported in a number of cancer types.3 Although more broadly effective and manageable than the traditional and targeted cancer therapies, a significant proportion of patients display innate resistance and do not respond at all to PD1/PDL1 blockade or they acquire therapeutic resistance over time.4,5 Therefore there is a need to determine the requirements for optimal T-cell rescue not only to improve current therapies but to also identify predictive biomarkers.6