Yanying Xu’s scientific contributions

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Publications (1)


The evaluation of TIGIT expression on both Foxp3⁻CD4⁺ and Foxp3⁺CD4⁺ T cell populations was undertaken. In a cohort of mice (n = 6), each receiving an i.p. injection of 1 × 10⁶ ID8 cells, peritoneal lavage fluid and spleen samples were collected seven days post-injection from both ovarian cancer and normal mice (n = 6). Mononuclear cells were isolated via Ficoll-Paque density gradient centrifugation. Flow cytometry was utilized to assess the proportions of TIGIT⁺Foxp3⁺CD4⁺ and TIGIT⁺Foxp3⁻CD4⁺ lymphocytes within the spleen and ascites (A). Additionally, the frequency of TIGIT⁺ cells within Foxp3⁺ and Foxp3⁻ CD4⁺ T cell subpopulations found in the spleen and ascites was examined (B). The results are depicted as means ± standard deviation. OC, ovarian cancer
Enhanced Immunosuppression by TIGIT⁺CD4⁺Tregs Compared to TIGIT⁻CD4⁺Tregs. Groups of mice (six individuals per group) were subjected to i.p. injection with 1 × 10⁶ ID8 cells. Ten days following injection, splenic TIGIT⁺CD4⁺Foxp3⁺ Tregs and TIGIT⁻CD4⁺Foxp3⁺ Tregs were isolated through flow sorting techniques from various experimental groups. These isolated cells were subsequently co-cultured with normal effector T cells (CD4⁺CD25⁻ T cells) sourced from healthy mice. The co-cultures were stimulated with anti-CD3 (5 µg/mL) and anti-CD28 (2 µg/mL) at a 1:1 ratio for a duration of 24 h. Proliferation (A), apoptotic rate (B), and the secretory potential (IFN-γ and IL-4) (C and D) of CD4⁺CD25⁻ T cells were assessed and quantified. The results are represented as means ± standard deviation
Profiling Tumor-Infiltrating Lymphocytes in ovarian cancer Mice Over Time. Tumor-infiltrating lymphocytes were harvested from ovarian cancer mice induced by ID8 cells at distinct time points following implantation and subsequently analyzed using flow cytometry. On the 10th (n = 3), 15th (n = 3), 20th (n = 3), and 25th (n = 3) days post-modeling, tumor volumes were measured. (A) The figure illustrates the frequency of TIGIT⁺ and TIGIT⁻ cells within the Foxp3⁺CD4⁺ T cell population in tumor-infiltrating lymphocytes. The r² values for TIGIT⁺ and TIGIT⁻ Tregs are 0.9258 and 0.9258, respectively. (B) The panel showcases the frequency of different subpopulations among CD8⁺ tumor-infiltrating lymphocytes expressing TIGIT and PD-1. Specifically, for CD8⁺TIGIT⁺PD-1⁺ T cells, the r² is 0.9380; for CD8⁺TIGIT⁻PD-1⁺ T cells, the r² is 0.2389, and for CD8⁺TIGIT⁻PD-1⁻ T cells, the r² is 0.4726
Profound Alterations in expression of PD-1 on CD8⁺ T Cell Accumulation within the Tumor Microenvironment upon Foxp3⁺ T Cell Depletion. In this experiment, DEREG mice (six individuals per group) were injected intraperitoneally with 1 µg DT or PBS 24 h before 1 × 10⁶ ID8 cells injection. Subsequently, 1 µg DT was administered on day 7 following tumor implantation. Control mice were treated with PBS injection. (A and B) On day 14 post DT or PBS injection, we sacrificed tumor-bearing mice that had received either PBS or DT treatment. Tumor-infiltrating lymphocytes were isolated and analyzed via FACS. The frequencies of CD8⁺TIGIT⁺PD-1⁺ (9.248 ± 1.518 vs. 20.52 ± 1.439, p < 0.01) and CD8⁺TIGIT⁻PD-1⁺ (8.482 ± 0.6521 vs. 19.95 ± 1.583, p < 0.01) tumor-infiltrating lymphocytes were calculated, comparing PBS control with DT-treated tumor-bearing mice. (C) The impact of Foxp3⁺ Tregs depletion on tumor growth is depicted (Mean ± SD, n = 4), p = 0.1502 on day 10, p = 0.0018 on day 15, p = 0.001 on day 20, p = 0.0004 on day 25. All data were collected from three independent experiments, and the results are presented as means ± standard deviation
Effects of Foxp3⁺ T cells depletion and anti-TIGIT antibodies on tumor growth. ID8 cells (1 × 10⁶) were injected i.p. in mice expressing the DTR under the control of the Foxp3 promoter (Foxp3-DTR mice) and either 1 µg DT or PBS was injected on day 12 post-tumor implantation. The anti-TIGIT mAb (clone 1B4) (100 µg) or an isotype-matched control antibody (cIg) (Ultra-LEAF™ Purified Mouse IgG1, κ Isotype Ctrl Antibody, Catalog #401414, BioLegend, San Diego, CA) or with anti-TIGIT mAb (absolute IgG1 antibody, clone 1B4, Catalog #Ab01258, BioLegend, San Diego, CA) was given every 4 days from day 12 to day 24 post-tumor implantation. Tumor sizes are represented as means ± standard deviation, PBS + clg vs. PBS + Anti-TIGIT, p = 0.0877 on day 10, p = 0.0075 on day 15, p = 0.1078 on day 20, p = 0.0575 on day 25; PBS + clg vs. DT + clg, p = 0.0170 on day 10, p = 0.0002 on day 15, p = 0.0029 on day 20, p = 0.0004 on day 25; DT + clg vs. DT + Anti-TIGIT, p = 0.0408 on day 10, p = 0.0012 on day 15, p = 0.0009 on day 20, p < 0.0001 on day 25. Experiments have been repeated twice. statistical differences were calculated by Mann-Whitney analyses at the indicated time points
TIGIT CD4 regulatory T cells enhance PD-1 expression on CD8 T cells and promote tumor growth in a murine ovarian cancer model
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December 2024

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Journal of Ovarian Research

Fengzhen Chen

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Yanying Xu

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Xiangyu Liu

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Lei Tian

Immune checkpoint-based immunotherapy has shown limited efficacy in the treatment of ovarian cancer. In recent years, the emergence of immune checkpoint co-targeting therapies, led by the combination targeting of TIGIT and FAK, has shown promise in ovarian cancer treatment. Our preliminary research indicates that TIGIT is predominantly expressed in regulatory T cells during ovarian cancer. However, the therapeutic impact of TIGIT targeting based on regulatory T cells in ovarian cancer remains to be elucidated. We utilized ID8 cells to establish a mouse model of ovarian cancer. Through flow cytometry and co-culture methods, we validated the relationship between the functionality of regulatory T cells and tumor masses, and confirmed the crucial role of TIGIT in immune suppression in ovarian cancer. Furthermore, using Foxp3-diphtheria toxin receptor (DTR) mice, we substantiated that the combined TIGIT antibody treatment, based on targeting regulatory T cells, effectively slowed down the progression of ovarian cancer. Taken together, our results have demonstrated that dual targeting of regulatory T cells and TIGIT effectively retards tumor growth, laying the groundwork for the clinical application of immune checkpoint combination therapies. Future research in ovarian cancer immunotherapy is leaning towards a strategy that combines multiple targets, and specific cell-type immunotherapies. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-024-01578-y.

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