Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Article Title: Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

doi: 10.1016/j.radonc.2023.109981

Figure Lengend Snippet: Fig. 2. Antitumor effects of triple-combination therapy of RT, anti-GITR agonist and PD-L1 blockade using an in vivo syngenic murine triple negative breast cancer model. (A) Treatment schedule for mice treated with RT, anti-GITR agonist and PD-L1 blockade. (B) Mean tumor volume of subcutaneous implants at hind limb (left) and flank (right) in mice of each treatment group: Control, agonistic anti-GITR antibody, PD-L1 blockade, RT, agonist anti-GITR antibody + PD-L1 blockade, agonist anti-GITR antibody + RT, PD-L1 blockade + RT and triple-combination therapy. (n = 5 mice per group) (C) The representative samples of lung with metastatic nodules and lung metastasis nodule count by each treatment group. (D) The representative bioluminescence images of subcutaneous nodules before and after each treatment, after subcutaneous injection of 4T1-luc tumor cells. The relative tumor burden of each treatment group is quantified by measuring the luminous intensity of photons emitted from each tumor in the images. (E) Representative images of lung samples with metastatic nodules indicated with an arrow and counts grouped by treatment. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001; RT, radiation therapy; αGITR, agonist anti-GITR antibody; αPD-L1., PD-L1 blockade.

Article Snippet: The anti-PD-L1 blocking antibody (5 mg/kg; BioXCell, BE0101) and the anti-GITR agonistic antibody (5 mg/kg; BioXCell, BE0063) were intraperitoneally injected on days 10, 12, 14, 17, and on days 11, 13, 15, 17, 19, and 21, respectively.

Techniques: In Vivo, Control, Injection

Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Article Title: Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

doi: 10.1016/j.radonc.2023.109981

Figure Lengend Snippet: Fig. 3. Profile of CD8+ cytotoxic T-cells in the tumor microenvironment according to treatment groups. (A) Flow cytometry analysis and immunohistochemistry results for CD8+ cytotoxic T-cells (CD3+ CD8+) (B) in the whole tumor microenvironment, (C) intratumoral region, (D) tumor periphery, and (E) in the stromal region are presented, respectively. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. RT, radiation therapy; αGITR, agonist anti-GITR antibody; αPD-L1, PD- L1 blockade.

Article Snippet: The anti-PD-L1 blocking antibody (5 mg/kg; BioXCell, BE0101) and the anti-GITR agonistic antibody (5 mg/kg; BioXCell, BE0063) were intraperitoneally injected on days 10, 12, 14, 17, and on days 11, 13, 15, 17, 19, and 21, respectively.

Techniques: Flow Cytometry, Immunohistochemistry

Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Article Title: Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

doi: 10.1016/j.radonc.2023.109981

Figure Lengend Snippet: Fig. 4. Profile of regulatory T-cells (Treg) in the tumor microenvironment according to treatment groups. (A) Flow cytometry analysis and (B) immunohisto chemistry results for Tregs (CD25+ Foxp3+) are presented, respectively. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. RT, radiation therapy; αGITR, agonist anti-GITR antibody; αPD-L1, PD-L1 blockade; Treg, regulatory T-cells.

Article Snippet: The anti-PD-L1 blocking antibody (5 mg/kg; BioXCell, BE0101) and the anti-GITR agonistic antibody (5 mg/kg; BioXCell, BE0063) were intraperitoneally injected on days 10, 12, 14, 17, and on days 11, 13, 15, 17, 19, and 21, respectively.

Techniques: Flow Cytometry, Immunohistochemistry

Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Article Title: Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

doi: 10.1016/j.radonc.2023.109981

Figure Lengend Snippet: Fig. 5. Immune cell profiles in the spleen according to treatment groups analyzed by flow cytometry. (A,B,C) Flow cytometric analysis results for (A) CD8+ cytotoxic T-cells, and (B) Effector memory T-cells (CD44high CD62Llow) and (C) Tregs (CD25+ Foxp3+) of the spleen are presented, respectively. * P < 0.05; ** P < 0.01; *** P<0.001; **** P < 0.0001. RT, radiation therapy; αGITR, agonist anti-GITR antibody; αPD-L1, PD-L1 blockade; Treg, regulatory T-cells.

Article Snippet: The anti-PD-L1 blocking antibody (5 mg/kg; BioXCell, BE0101) and the anti-GITR agonistic antibody (5 mg/kg; BioXCell, BE0063) were intraperitoneally injected on days 10, 12, 14, 17, and on days 11, 13, 15, 17, 19, and 21, respectively.

Techniques: Flow Cytometry

Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Article Title: Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

doi: 10.1016/j.radonc.2023.109981

Figure Lengend Snippet: Fig. 6. Production of interferons in plasma. Serum levels of (A) interferon-beta and (B) interferon–gamma at 1 week after administration of RT. * P < 0.05; ** P < 0.01; *** P < 0.001. CON, contrast; RT, radiation therapy; αGITR, agonist anti-GITR antibody; αPD-L1, PD-L1 blockade.

Article Snippet: The anti-PD-L1 blocking antibody (5 mg/kg; BioXCell, BE0101) and the anti-GITR agonistic antibody (5 mg/kg; BioXCell, BE0063) were intraperitoneally injected on days 10, 12, 14, 17, and on days 11, 13, 15, 17, 19, and 21, respectively.

Techniques: Clinical Proteomics