Review
. 2021 Sep; 13(18):.
doi: 10.3390/cancers13184616.

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

Yasuhiro Kanda 1 Taku Okazaki 2 Tomoya Katakai 1 
Affiliations
  • PMID: 34572844
  •     165 References

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.

Keywords: CTLA-4; PD-1; T cell motility; immune checkpoint blockade; tumor-draining lymph node.

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SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation.
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TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion.
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Lymph Node Subcapsular Sinus Macrophages as the Frontline of Lymphatic Immune Defense.
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Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection.
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Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
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Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model.
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Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects.
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J Immunol, 2014 Jun 18; 193(2). PMID: 24935929
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CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma.
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Qi Peng, Xiangyan Qiu, +8 authors, Haidong Tang.
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Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects.
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The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells.
Francesco Marangoni, Thomas T Murooka, +4 authors, Thorsten R Mempel.
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