Cancer is primarily a disease of the older adult with more than 50 % of new cases occurring in adults older than 65 years. The care of older adults with cancer can be complicated by multiple issues such as comorbidity, age-related organ dysfunction, and decreased functional status. This “vulnerable” profile underlines the importance of understanding the role of different treatment modalities in the geriatric population. Immune checkpoint inhibitor is a novel treatment modality that is being explored in multiple malignancies.
Immune system activation begins when T cells recognize peptide fragments of intracellular proteins that are expressed on the surface of antigen presenting cells (APCs) bound to specific mixed histocompatibility complex (MHC) molecules. This interaction requires the presence of a costimulatory molecule (B7) and it results in the in upregulation of cytotoxic Tlymphocyte antigen 4 (CTLA-4) on the surface of T lymphocytes. CTLA-4 is a negative regulator of T cell activation. It exerts its downregulating activity by forming a bond with B7 that outcompetes CD28, thus serving as a physiologic “brakeof” immune function. The programmed cell death 1 receptor (PD-1) is another inhibitory receptor on activated T cells. The ability of activated T cells to produce an effective immune response is decreased when PD-1 binds to its ligand PD-L1. PD-L1 is often present on tumor cells.