Motility Dynamics of T Cells in Tumor-Draining Lymph Nodes: A Rational Indicator of Antitumor Response and Immune Checkpoint Blockade

SIMPLE SUMMARY: Immune checkpoint blockade (ICB) therapies are attracting much attention for the clinical treatment of tumors. Combination therapies are being developed to enhance the effects of ICBs, and the importance of tumor-draining lymph nodes (TDLNs) has been reevaluated in antitumor responses via ICB therapy. The migration and motility status of T cells and their functional interaction with antigen-bearing dendritic cells are key factors for inducing adaptive immunity in LNs. Although immune checkpoint molecules are known to regulate T cell motility, their actual influence on T cell dynamics in TDLNs, particularly in ICBs, is poorly understood. In this review, we summarize the relevance of T cell dynamics and immune responses in draining LNs, and discuss the alteration of T cell motility under ICB. To develop better immunotherapies using ICBs, studying T cell dynamics in TDLNs can provide a good indicator to evaluate the efficacy of antitumor therapy. ABSTRACT: The migration status of T cells within the densely packed tissue environment of lymph nodes reflects the ongoing activation state of adaptive immune responses. Upon encountering antigen-presenting dendritic cells, actively migrating T cells that are specific to cognate antigens slow down and are eventually arrested on dendritic cells to form immunological synapses. This dynamic transition of T cell motility is a fundamental strategy for the efficient scanning of antigens, followed by obtaining the adequate activation signals. After receiving antigenic stimuli, T cells begin to proliferate, and the expression of immunoregulatory receptors (such as CTLA-4 and PD-1) is induced on their surface. Recent findings have revealed that these ‘immune checkpoint’ molecules control the activation as well as motility of T cells in various situations. Therefore, the outcome of tumor immunotherapy using checkpoint inhibitors is assumed to be closely related to the alteration of T cell motility, particularly in tumor-draining lymph nodes (TDLNs). In this review, we discuss the migration dynamics of T cells during their activation in TDLNs, and the roles of checkpoint molecules in T cell motility, to provide some insight into the effect of tumor immunotherapy via checkpoint blockade, in terms of T cell dynamics and the importance of TDLNs.