Extended Data Fig. 15 |. Siglec-7/9 degradation synergizes with CTLA-4 blockade in suppressing tumor growth in a PDAC tumor model.

a, Assessment of Siglec-7/-9 depletion in tumor-infiltrating immune cells (including TAMs, T cells and NK cells) in MT5 tumors in Sig7/9⁺ mice following intratumoral administration of Sig7/9de. b, Growth of individual subcutaneous MT5 tumors inoculated in SigE^KO (n= 5 mice per group) and Sig7/9⁺ (n= 5 mice per group) mice treated with PBS, Sig7/9de, and/or anti-CTLA-4. c, Rechallenge of the tumor-free mice from (b) with subcutaneous MT5 tumor cells in the opposing flanks (n = 2 in SigE^KO treated with anti-CTLA-4; n = 2 in Sig7/9⁺ co-treated with Sig7/9de and anti-CTLA-4). d,e, Examination of adoptive transfer of CD8⁺ T cells (isolated from MT5 tumor-cured Sig7/9⁺ mice or LCMV Arm-cleared WT mice) for the control of MT5 tumor growth in Sig7/9⁺ mice (n= 5 mice per group). Average sizes of primary tumors ± SEM are presented in cubic millimeters (mm³). f, Gating strategy for sorting tumor-infiltrating immune cells in MT5 tumors inoculated in Sig7/9⁺ mice treated with single PBS, anti-CTLA-4, Sig7/9de, and combination of Sig7/9de and anti-CTLA-4, in which, CD8⁺ T, CD4⁺ T, NK, F4/80⁺, Ly6C⁺ cells and DCs were characterized among live CD45⁺ population after gating out doublets and dead cells. Dendritic cell, DC. g, MT5 tumor weight in the MT5 tumor model in each treatment condition at day 18 (n= 5 mice per group). h, Flow cytometry analysis of numbers of tumor dLN-infiltrating immune cells in the MT5 tumor model in each treatment condition at day 18 (n= 5 mice per group). i, Assessment of in vivo MT5 tumor (GFP) phagocytosis by quantifying the percentage of GFP⁺ TAMs within tumor tissues from Sig7/9⁺ mice. Data are mean ± s.d. Two-tailed unpaired Student’s t-test (a,e,g,h,i).