Figure 7 from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma
Year: 2025
Type: other
Abstract: Effective PD-1 blockade requires Ly6G+ myeloid cells and CD8+ T cells. A, In AB12 tumors, αLy6G initiated 1.5 hours after PDT does not significantly change tumor response (P = 0.57; PDT/αLy6G shown as dark red dotted line). For PDT, n = 14 and for PDT/αLy6G, n = 13. PDT/αLy6G isotype control (n = 13) is also not significantly different from PDT/αLy6G (P = 0.17) or from PDT alone (P = 0.65). B, In TI/PDT-treated mice, Ly6G depletion did not significantly impact the time for tumors to regrow to 400 mm3 (TI/PDT/αLy6G, n = 14, shown as pink line) The TI/PDT/αLy6G isotype control group (n = 14) is similar (P = 0.81 compared with TI/PDT/αLy6G and P = 0.42 compared with TI/PDT). C, In TI/PDT-treated mice that also received αPD-1, Ly6G depletion led to a rapid and significant decrease in mice with tumors <400 mm3 (P < 0.0002; TI/PDT/αPD-1/αLy6G, n = 13, shown as dark blue dotted line). The TI/PDT/αPD-1/αLy6G isotype control group (n = 12) is similar to TI/PDT/αPD-1 (P = 0.80) and has significantly longer survival than TI/PDT/αPD-1/αLy6G (P < 0.001). D, Flow cytometric analysis of tumor-infiltrating lymphocytes 1 day after TI/PDT/αPD-1 demonstrated that Ly6G depletion after TI/PDT/αPD-1 did not significantly change the percentage of Ly6C+ cells in the tumor (P = 0.73, left, n = 7 tumors for TI/PDT/αPD-1 and n = 6 tumors for TI/PDT/αPD-1/αLy6G). However, Ly6G depletion led to a significant increase in the PD-L1 expression on the Ly6C+ cells (P = 0.014, right). E, In AB12 tumors, CD8 depletion (TI/PDT/αPD-1/αCD8, n = 11, shown as pink lines) led to rapid tumor regrowth (P <0 .001 compared with TI/PDT/αPD-1). The TI/PDT/αPD-1/αCD8 isotype control group (n = 12) is similar to TI/PDT/αPD-1 (P = 0.89) and has significantly longer survival than TI/PDT/αPD-1/αCD8 (P < 0.001). F, Similarly in AE17O tumors, CD8 depletion (TI/PDT/αPD-1/αCD8, n = 10) also led to rapid tumor regrowth (P = 0.033 compared with TI/PDT/αPD-1). The TI/PDT/αPD-1/αCD8 isotype control group (n = 10) is similar to TI/PDT/αPD-1 (P = 0.24) and has significantly longer survival than TI/PDT/αPD-1/αCD8 (P < 0.001). Groups treated with an isotype for αLy6G or αCD8 are plotted in pale orange. Tumor responses are compared using log-rank (Mantel–Cox) tests, and all other statistical tests are by Mann–Whitney.
Authors: Gwendolyn M. Cramer, Richard W. Davis, Emmanouil Papasavvas, Astero Klampatsa, Joann M. Miller, Shirron Carter, Ruth Ikpe, Min Yuan, Sandy Widura, R. Sonali Majumdar, Sally McNulty, Mary Putt, Andrew V. Kossenkov, Luis J. Montaner, Sunil Singhal, Edmund K. Moon, Steven M. Albelda, Keith A. Cengel, Theresa M. Busch
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410618831