CD155-Transducing Signaling through TIGIT Plays an Important Role in Transmission of Tolerant State and Suppression Capacity

Negishi, Naoko; Sato, Takehito; Yamashita-Kanemaru, Yumi; Shibuya, Kazuko; Uchida, Koichiro; Kametani, Yoshie; Yagita, Hideo; Kitaura, Jiro; Okumura, Ko; Habu, Sonoko

doi:10.4049/immunohorizons.1800033

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…5. TIGIT on memory B cells could directly act on CD155 expressed on activated T cells 32,33 , resulting in the suppression of T cell response. Furthermore, TIGIT expressed on human memory B cells can also effectively suppress DC maturation via the ligation of CD155 expressed on DCs, resulting in the suppression of their proinflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Implication of TIGIT+ human memory B cells in immune regulation

et al. 2021

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Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation.

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Section: Discussionmentioning

confidence: 99%

Implication of TIGIT+ human memory B cells in immune regulation

et al. 2021

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“…Severely immunodeficient NOG mice (NOD/Shi-scid, IL-2Rγ deficient) were purchased from Central Institute for Experimental Animals. C57BL/6 Cd226 −/− and Tigit −/− mice were generated as previously described (Iguchi-Manaka et al, 2008; Negishi et al, 2018). Cd96 −/− mice were generated by using a CRISPR-Cas9 system, as follows.…”

Section: Methodsmentioning

confidence: 99%

Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells

Okumura

Iguchi-Manaka

Murata

et al. 2020

Journal of Experimental Medicine

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CD155 is a ligand for DNAM-1, TIGIT, and CD96 and is involved in tumor immune responses. Unlike mouse cells, human cells express both membranous CD155 and soluble CD155 (sCD155) encoded by splicing isoforms of CD155. However, the role of sCD155 in tumor immunity remains unclear. Here, we show that, after intravenous injection with sCD155-producing B16/BL6 melanoma, the numbers of tumor colonies in wild-type (WT), TIGIT knock-out (KO), or CD96 KO mice, but not DNAM-1 KO mice, were greater than after injection with parental B16/BL6 melanoma. NK cell depletion canceled the difference in the numbers of tumor colonies in WT mice. In vitro assays showed that sCD155 interfered with DNAM-1–mediated NK cell degranulation. In addition, DNAM-1 had greater affinity than TIGIT and CD96 for sCD155, suggesting that sCD155 bound preferentially to DNAM-1. Together, these results demonstrate that sCD155 inhibits DNAM-1–mediated cytotoxic activity of NK cells, thus promoting the lung colonization of B16/BL6 melanoma.

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“…TIGIT binds to nectin and nectin-like (NECL) adhesion molecules, including NECTIN-2 (CD112) ( 52 , 53 ), NECTIN-3 (CD113) ( 45 , 51 ), and NECL-5 (CD155) ( 54 ) to mediate cell adhesion and signaling.…”

Section: Overview Of Tigit Structure and Ligandsmentioning

confidence: 99%

“…TIGIT–CD155 in CD8 + T cells induces immunosuppression via the NF-κB signaling pathway, promoting a tolerant state that is passed down across T cell generation. In this process, CD155 + naïve T cells trans-interact with TIGIT + preceding tolerant T cells resulting in increased TIGIT expression and IL-2 suppression via Blimp1 increment ( 54 , 103 ).…”

Section: Tigit Pathways and Immune Cells Involvedmentioning

confidence: 99%

Update in TIGIT Immune-Checkpoint Role in Cancer

2022

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The in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT.

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CD155-Transducing Signaling through TIGIT Plays an Important Role in Transmission of Tolerant State and Suppression Capacity

Cited by 8 publications

References 30 publications

Implication of TIGIT+ human memory B cells in immune regulation

Implication of TIGIT+ human memory B cells in immune regulation

Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells

Update in TIGIT Immune-Checkpoint Role in Cancer

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