Exploring Biomechanical Regulation on Anti-tumor Immunity of CD8 T+ Cells by Using Ptpn21 Knock-out Mouse Model Público
Chen, Angela (Spring 2025)
Abstract
The role of biomechanical regulation in CD8+ T cell function has not been well characterized. In this study, we aim to examine the biomechanical properties of CD8+ T cells by using wildtype (+/+, WT) and knock-out Ptpn21 (-/-, KO) mouse models. Firstly, we observed marked differences in stiffness by using atomic force microscopy, where Ptpn21 KO CD8+ T cells exhibited reduced biomechanical rigidity compared to the WT ones. Due to this reduced stiffness, KO CD8+ T cells demonstrated an enhanced capacity to deform and transmigrate through narrow pores in Transwell migration assay.
Mechanical softness in Ptpn21 KO CD8+ T cells correlates with functional impairments, evidenced by reduced activation responses following acute αCD3/CD28 stimulation. Additionally, lower proportion of Ptpn21 KO CD8+ T cells differentiates into central memory T cells, suggesting compromised immune memory formation. Analysis of exhaustion markers revealed a decreased level of exhaustion markers in Ptpn21 KO CD8+ T cells, highlighting a link between mechanical softness and reduced cellular effector functions. Supporting in vivo experiments demonstrate impaired circulation of Ptpn21 KO CD8+ T cells within the lymphatic system, with significantly fewer cells found in circulation and primary lymphoid organs post- transfer. In conclusion, the mechanical softness may hinder effective antigen presentation and subsequent activation of CD8+ T cells in vivo under tumor bearing microenvironment as well.
Our findings underscore the importance of biomechanical integrity in preserving the optimal function of CD8+ T cells. The loss of this integrity initiates a cascade of functional deficiencies, notably impaired activation. The results reveal the role of biomechanical regulation in CD8+ T cell functionality and suggest potential therapeutic directions for enhancing T cell responses.
Table of Contents
Table of Content:
TABLE OF FIGURES ···························································································································2
INTRODUCTION ·································································································································3
RESULTS················································································································································6
PTPN21 KO CD8+ T CELLS ARE BIOMECHANICALLY SOFTER, WITH A GREATER DEFORMABILITY, COMPARED TO WT ············ 6
SOFTER CD8+ T CELLS HAVE WEAKER RESPONSE TO NONSPECIFIC STIMULATION, SHOWING DECREASED ACTIVATION ····· 8
IN VIVO ADOPTIVE TRANSFER REVEALS THE LOSS OF CIRCULATION OF KO CD8+ T CELLS IN LYMPHATIC SYSTEM ·············· 11
DISCUSSIONS AND FUTURE DIRECTION ················································································· 16
METHODOLOGY ····························································································································· 20
ACCOMPLISHMENT························································································································ 24
REFERENCE ······································································································································ 25
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Exploring Biomechanical Regulation on Anti-tumor Immunity of CD8 T+ Cells by Using Ptpn21 Knock-out Mouse Model () | 2025-04-18 11:02:05 -0400 |
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