Evaluating The Expression Patterns Of Multiple Inhibitory Receptors Associated With T-Cell Exhaustion Using Multicolor Flow Cytometry

By Mirko Corselli and Suraj Saksena

T-cell exhaustion is a critical phenomenon that arises from persistent antigen stimulation, leading to a decline in the functionality of CD8+ T cells. Initially recognized in chronic viral infections, such as HIV and hepatitis, this state of dysfunction has significant implications for cancer immunotherapy, particularly in the context of non-small cell lung cancer. The hallmark of exhausted T cells is the upregulation of inhibitory receptors, including PD-1 and CTLA-4, which hinder T-cell activation and contribute to immune evasion by tumors.

This study employs a sophisticated 12-color flow cytometry panel to meticulously analyze the expression patterns of various inhibitory receptors across distinct T-cell subsets. By utilizing fresh peripheral blood mononuclear cells (PBMCs) and cultured T cells, researchers uncover unique receptor expression profiles that evolve with T-cell differentiation and stimulation. Notably, the investigation reveals that while certain receptors like TIGIT are absent in naïve T cells, they become prominent in specific memory subsets, indicating a nuanced landscape of T-cell responses under chronic stimulation. The findings underscore the necessity for comprehensive immunophenotypic analyses to enhance the effectiveness of CAR T-cell therapies and other immunotherapeutic strategies. By elucidating the intricate dynamics of T-cell exhaustion and inhibitory receptor expression, this research paves the way for innovative therapeutic approaches aimed at rejuvenating T-cell function in cancer and chronic infections.