Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Immune Cytolytic Activity and Strategies for Therapeutic Treatment

Version 1 : Received: 31 January 2024 / Approved: 31 January 2024 / Online: 31 January 2024 (12:32:26 CET)

A peer-reviewed article of this Preprint also exists.

Agioti, S.; Zaravinos, A. Immune Cytolytic Activity and Strategies for Therapeutic Treatment. Int. J. Mol. Sci. 2024, 25, 3624. Agioti, S.; Zaravinos, A. Immune Cytolytic Activity and Strategies for Therapeutic Treatment. Int. J. Mol. Sci. 2024, 25, 3624.

Abstract

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

Keywords

Cytolytic Activity (CYT); Tumor-Infiltrating Lymphocytes (TILs); Gene Expression Profiling; Spatial Analysis Techniques; Immune Checkpoint Pathways; Tumor Microenvironment (TME); Antigen Presentation; Metabolic Pathways

Subject

Biology and Life Sciences, Immunology and Microbiology

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