A Fundamental Theory for Dexterous Surgical Skills Transfer to Medical Robots
Abstract
Chronic diseases like cancers that evade the immune system continue to impact the lives of millions of patients worldwide causing high morbidity and mortality as well as significant economic burden. It is now evident that in melanoma tumors, persisting antigen results in the development of dysfunctional or exhausted anti-tumor T cells (Texs). Continuous TCR stimulation and multiple suppressive mechanisms limit effector T cell functions, including high expression and signaling of multiple inhibitory receptors (e.g., PD-1, CTLA- 4, Lag3, Tim3) including PSGL-1 (P-selectin glycoprotein ligand-1), which we identified. Therapeutic success targeting these inhibitory checkpoints (PD-1/PDL-1 and CTLA-4) using blocking antibodies can reinvigorate Texs and improve pathogen and tumor control in mice and patients. These drugs are now standard treatment for melanoma, but at present are only effective in a subset of patients, highlighting the need to identify additional inhibitory pathways that can be targeted to improve patient outcomes. Our purpose is to understand when PSGL-1 signaling is required to establish T cell exhaustion and in what cell types PSGL-1 contributes to inhibition of T cell function. We will also understand whether PSGL-1 can be targeted to reverse T cell exhaustion to promote tumor control.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2022
- Accession Number
- AD1191522
Entities
People
- Juan Pablo Wachs
Organizations
- Purdue University