Page 1167 - Veterinary Immunology, 10th Edition

T cells. This also results in a loss of T cell function and eventual T
VetBooks.ir cell “exhaustion.”

Checkpoint inhibitors can block these proteins, reverse T cell
exhaustion, and so permit T cell tumor destruction to proceed (Fig.

35.6). These inhibitors are monoclonal antibodies whose targets
include programmed cell death protein 1 (PD-1) and its ligand, PD-
L1 (pembrolizumab and nivolumab). A second T cell inhibitory
pathway uses the T cell receptor cytotoxic T-lymphocyte–associated

protein 4 (CTLA-4). CTLA-4 is normally expressed on T cell
surfaces following activation (Chapter 14). Its ligands are CD80 and
86 expressed on antigen-presenting cells, and its role is to prevent
uncontrolled T cell activation. CTLA-4 expressed on cancer cells

will prevent their destruction. Monoclonal antibodies against
CTLA-4 (ipilimumab) will block this suppressive pathway and
permit cancer cell destruction. Checkpoint inhibitors have achieved
remarkable success in the treatment of metastatic melanomas,

kidney and lung tumors, and hematologic cancers. A combination
of anti–PD-1 and anti–CTLA-4 appears to be exceptionally effective
in permitting T cell cytotoxicity to proceed and results in long-term
remissions.

1167