Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
St. Jude Children's Research Hospital · Johns Hopkins University · +3 more institutions
Abstract
Inhibitory receptors on immune cells are pivotal regulators of immune escape in cancer. Among these inhibitory receptors, CTLA-4 (targeted clinically by ipilimumab) serves as a dominant off-switch while other receptors such as PD-1 and LAG-3 seem to serve more subtle rheostat functions. However, the extent of synergy and cooperative interactions between inhibitory pathways in cancer remain largely unexplored. Here, we reveal extensive coexpression of PD-1 and LAG-3 on tumor-infiltrating CD4(+) and CD8(+) T cells in three distinct transplantable tumors. Dual anti-LAG-3/anti-PD-1 antibody treatment cured most mice of established tumors that were largely resistant to single antibody treatment. Despite minimal…
Citation impact
- FWCI
- 15.61
- Percentile
- 100%
- References
- 51
Authors
21- SWSeng‐Ryong Woo
St. Jude Children's Research Hospital, Johns Hopkins University, Bristol-Myers Squibb (United States), Sidney Kimmel Comprehensive Cancer Center, Stanford University
- MEMeghan E. Turnis
St. Jude Children's Research Hospital, Johns Hopkins University, Bristol-Myers Squibb (United States), Sidney Kimmel Comprehensive Cancer Center, Stanford University
- MVMonica V. Goldberg
St. Jude Children's Research Hospital, Johns Hopkins University, Bristol-Myers Squibb (United States), Sidney Kimmel Comprehensive Cancer Center, Stanford University
- JBJaishree Bankoti
St. Jude Children's Research Hospital, Johns Hopkins University, Bristol-Myers Squibb (United States), Sidney Kimmel Comprehensive Cancer Center, Stanford University
- MSMark Selby
St. Jude Children's Research Hospital, Johns Hopkins University, Bristol-Myers Squibb (United States), Sidney Kimmel Comprehensive Cancer Center, Stanford University
Topics & keywords
- Immune system
- Cancer
- Cancer research
- Receptor
- Antibody
- Immunology
- Ipilimumab
- Biology
- Good health and well-being