Title : Profiling of immune check point inhibitors (Tim-3, LAG-3, TIGIT, PD-1 and CTLA-4) in gallbladder cancer
Abstract:
Introduction: Gallbladder cancer is the 5th most common gastrointestinal cancer. Early diagnosis is not generally possible. The outlook is poor for recovery if the cancer is found after symptoms have started to occur, with a 5-year survival rate of close to 3%. The prognosis still remains poor. A number of therapeutic approaches, owing to the creation of advanced technological measures (e.g., next-generation sequencing, transcriptomics, proteomics), have been intensively innovated, including targeted therapy and immunotherapy. In the present study, we primarily focus on the targeted therapy capable of specifically inhibiting individual immune checkpoint inhibitors, e.g., Tim-3, LAG-3, TIGIT, PD-1, and CTLA-4 molecules that govern aberrant signaling cascades in GBC.
Methods: Only confirmed Gall bladder cancer patients were recruited in this study at the Department of Surgical Oncology/pathology, All India Institute of Medical Sciences (AIIMS), New Delhi. Both tissue and blood samples were taken from patients. Samples were processed accordingly for flow cytometric analysis. Flow cytometry was performed for Tim-3, LAG-3, TIGIT, PD-1, and CTLA-4 checkpoint inhibitor molecules.
Results: Expression of checkpoint inhibitory molecules differed between patients. Co-expression of TIGIT and PD-1 were found to be common in patients. A few patients also showed high co-expression of TIM-3 and PD-1. Only 2 patients showed a high expression profile for CTLA-4 and LAG-3.