Pan-cancer analysis of co-inhibitory molecules reveals their potential prognostic and clinical values as biomarkers

Abstract

Abstract The widespread use of immune checkpoint inhibitors (anti-CTLA4 or PD-1) has opened a new chapter in tumor immunotherapy by providing long-term survival for patients. Unfortunately, these agents are not universally available and only a small portion of patients respond to them. Therefore, there is an urgent need to develop novel therapeutic strategies targeting other co-inhibitory molecules, such as LAG3, TIM3, TIGIT, NRP1, VISTA. In addition, combination therapies including combined blockade and chemo-immunotherapy are promising topics in this field, such as the recent FDA approval of combination therapy targeting both LAG3 and PD-1. However, comprehensive information on the expression and prognostic value of co-inhibitory molecules, including co-inhibitory receptors and their ligands, in different cancers is not yet available. For this reason, we performed this analysis to assess the expression patterns and correlations of co-inhibitory molecules, and further evaluated their relationships with patient prognosis, tumor microenvironment and drug sensitivity. These co-inhibitory molecules have the potential to be prognostic biomarkers and drivers of individualized therapy for a wide range of cancers, as they are closely associated with these metrics.