Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma

Brauneck, Franziska; Weimer, Pauline; Wiesch, Julian Schulze zur; Weisel, Katja; Leypoldt, Lisa; Vohwinkel, Gabi; Fritzsche, Britta; Bokemeyer, Carsten; Wellbrock, Jasmin; Fiedler, Walter

doi:10.3389/fmed.2021.763773

Cited by 25 publications

(29 citation statements)

References 69 publications

(109 reference statements)

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“…In both myeloid leukemia and multiple myeloma, using flow cytometry, the bone marrow resident γδ T cells, a T cell subpopulation of non-MHC-restricted, have shown TIGIT, PD-1, TIM3, and the ectonucleoside triphosphate diphosphohydrolase-1 (CD39) co-expression at a high level compared to αβ T cell but similar to that expressed on CD8 + effector T cells ( 139 ). These markers were linked to signs of exhaustion, such as transcriptional reprogramming, decreased release of proinflammatory cytokines, decreased T cell proliferation, and lesser tumoricidal activity, and were associated with a lower OS for myeloid leukemia ( 139 , 140 ).…”

Section: Tigit In Cancer Progressionmentioning

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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Section: Tigit In Cancer Progressionmentioning

confidence: 99%

Update in TIGIT Immune-Checkpoint Role in Cancer

2022

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“…Although γδ T cells were applied to adoptive cell therapy of ccRCC for decades, studies for the identification of autologous tumor‐reactive γδ T cells have been limited. Previous studies 13,18,19 and our bioinformatic analysis indicated that ccRCC patients with high TIGIT expression showed stronger antitumor response.In the further study, we demonstrated that the TIGIT expression is associated with the activation of γδ T cells triggered by ZOL. More interestingly, TIGIT + γδ T cells exhibited enhanced activation, stronger tumor reactivities and higher cytotoxicity when challenged by tumor cells.…”

Section: Discussionmentioning

confidence: 64%

TIGIT-expressing zoledronate-specific γδ T cells display enhanced antitumor activity

You

Zhu

Zhao

et al. 2022

Journal of Leukocyte Biology

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Human γδ T cells hold a pivotal role in tumor immunosurveillance through their prompt activation and cytokine secretion and have received much attention in adoptive immunotherapy of clear cell renal cell carcinoma (ccRCC). However, the therapeutic effects are limited in ccRCC. Therefore, it is now critical to improve therapeutic strategies based on γδ T cells, especially identification of functional γδ T cell subsets. In this study, we aimed to identify γδ T cells that might have enhanced responses against ccRCC. Bioinformatic analysis showed that ccRCC patients with high T cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) expression had higher levels of effector molecules. Then, we examined the changes in the TIGIT+ γδ T cell percentages of 6 ccRCC patients and 14 healthy subjects through zoledronate (ZOL) stimulation. Results indicated that percentages of TIGIT+ γδ T cells were positively correlated with activated γδ T cells in early activation stage. Further study demonstrated that TIGIT+ γδ T cells exhibited enhanced activation, contained more terminally differentiated effector γδ T cells and produced higher cytokine compared with TIGIT‐ γδ T cells. Finally, we investigated the functions and found that TIGIT+ γδ T cells exhibited stronger tumor reactivities and higher cytotoxicity when challenged by tumor cells. Above results imply that TIGIT+ γδ T cells are the main effectors in ZOL recognition and tumor cells challenging. The results of the present study serve as basis for future functional studies on TIGIT+ γδ T cells and provide a promising approach of immunotherapy in ccRCC.

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“…We chose NDMM as a control group to avoid the impact of other drugs given before DARA on the BM microenvironment. Brauneck et al found that CD8 + T-cells from NDMM showed an increased expression of PD-1 and TIGIT compared to healthy controls [ 34 ]. As we did not include a group of healthy controls, we were unable to perform the same comparison; however, we found no correlation between the expression of checkpoint molecules on CD8 + T-cells and response to first line treatment.…”

Section: Discussionmentioning

confidence: 99%

High Expression of the Costimulatory Checkpoint Factor DNAM-1 by CD4+ T-Cells from Multiple Myeloma Patients Refractory to Daratumumab-Containing Regimens

et al. 2022

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Multiple myeloma is an incurable disease characterized by unregulated growth of malignant plasma cells in the bone marrow (BM). Tumor-induced dysfunction of T-cells may be responsible for immune evasion and failure of immunotherapy. Therefore, a better understanding of the phenotype of T-cells at the tumor site is needed. We assessed the expression of immune regulatory receptors on T-cell subsets from peripheral blood (PB) and BM using multicolor flow cytometry. Paired PB and BM samples were collected from newly diagnosed, treatment-naïve myeloma patients (n = 19) and patients progressing during treatment with the CD38 monoclonal antibody daratumumab alone or in combination with other anti-myeloma drugs (n = 39). We observed that CD4+ T-cells from both PB and BM of patients relapsing on daratumumab have a higher expression of the costimulatory checkpoint receptor DNAM-1. The potential role of DNAM-1+CD4+ T-cells in the development of resistance to daratumumab needs further exploration. We also observed that the inhibitory checkpoint receptor TIGIT is more frequently expressed by BM CD8+ T-cells from myeloma patients than PD-1 and CTLA-4, which supports the hypothesis that TIGIT may play a central role in the immune escape of the malignant plasma cells.

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Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma

Cited by 25 publications

References 69 publications

Update in TIGIT Immune-Checkpoint Role in Cancer

Update in TIGIT Immune-Checkpoint Role in Cancer

TIGIT-expressing zoledronate-specific γδ T cells display enhanced antitumor activity

High Expression of the Costimulatory Checkpoint Factor DNAM-1 by CD4+ T-Cells from Multiple Myeloma Patients Refractory to Daratumumab-Containing Regimens

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