This section provides supplementary figures and data to support the main findings of the study. The figures cover various aspects of PD-L1 expression and its regulation in different cell lines and conditions: 1. **Figure S1** examines the differences in translation rates and protein degradation between PC3 and SK-MEL-28 cells, showing that these factors do not explain the discordance in mRNA and protein levels. It includes polysome profiles, mRNA distribution, and Western blot analyses of PD-L1 and related proteins. 2. **Figure S2** demonstrates that IFN-γ increases PD-L1 levels in both PC3 cells and exosomes without affecting the number of vesicles or exosomes. It includes Western blot and NanoSight measurements. 3. **Figure S3** investigates the effects of deleting Rab27a and nSMase2 in PC3 cells, showing changes in PD-L1 expression, cell counts, and mRNA levels. 4. **Figure S4** explores the origin of exosomal PD-L1, showing that it arises from endocytosis of cell surface PD-L1. It includes flow cytometry, confocal microscopy, and Western blot analyses. 5. **Figure S5** characterizes TRAMP-C2 cells with deleted Rab27a and nSMase2, showing changes in PD-L1 expression and secretion. 6. **Figure S6** provides immune profiling of spleen from mice with different genotypes, including CD8+, CD4+, and regulatory T cells. 7. **Figure S7** characterizes MC38 cells with deleted Pd-11 and Rab27a, showing changes in lymphocyte infiltration and vesicle secretion. It also includes survival curves of mice treated with GW4869. These figures collectively provide a comprehensive understanding of the mechanisms underlying PD-L1 expression and its regulation in various cellular contexts.This section provides supplementary figures and data to support the main findings of the study. The figures cover various aspects of PD-L1 expression and its regulation in different cell lines and conditions: 1. **Figure S1** examines the differences in translation rates and protein degradation between PC3 and SK-MEL-28 cells, showing that these factors do not explain the discordance in mRNA and protein levels. It includes polysome profiles, mRNA distribution, and Western blot analyses of PD-L1 and related proteins. 2. **Figure S2** demonstrates that IFN-γ increases PD-L1 levels in both PC3 cells and exosomes without affecting the number of vesicles or exosomes. It includes Western blot and NanoSight measurements. 3. **Figure S3** investigates the effects of deleting Rab27a and nSMase2 in PC3 cells, showing changes in PD-L1 expression, cell counts, and mRNA levels. 4. **Figure S4** explores the origin of exosomal PD-L1, showing that it arises from endocytosis of cell surface PD-L1. It includes flow cytometry, confocal microscopy, and Western blot analyses. 5. **Figure S5** characterizes TRAMP-C2 cells with deleted Rab27a and nSMase2, showing changes in PD-L1 expression and secretion. 6. **Figure S6** provides immune profiling of spleen from mice with different genotypes, including CD8+, CD4+, and regulatory T cells. 7. **Figure S7** characterizes MC38 cells with deleted Pd-11 and Rab27a, showing changes in lymphocyte infiltration and vesicle secretion. It also includes survival curves of mice treated with GW4869. These figures collectively provide a comprehensive understanding of the mechanisms underlying PD-L1 expression and its regulation in various cellular contexts.