Figure 7. Exogenously Introduced Exosomal PD-L1 Rescues Immune Suppression and Tumor Growth of Rab27a Null Tumors.
(A) Schematic of experimental design (B)–(K); briefly, mice were transplanted with 1 × 106 Rab27a null TRAMP-C2 cells, followed by 3 times per week tail-vein injections of exosomes that were collected from either WT or Pd-l1 null TRAMP-C2 cells grown in vitro. Immune analysis was performed at 14 days.
(B) Spleen weight in grams.
(C–E) Flow cytometric quantification of the percentage of CD45+ CD3+ cells that are CD8 (C), CD4 (D), and regulatory T cells (T-reg) (E), respectively, in the draining lymph node (DLN).
(F and G) Quantification of the percentage PD-1+ cells among the CD8 (F) and CD4 (G) T cell populations.
(H and I) Quantification of the percentage of Tim3+ cells among the CD8 (H) and CD4 (I) T cell populations.
(J and K) Quantification of the percentage of granzyme B (GzmB+) cells among the CD8 (J) and CD4 (K) T cell populations.
(B–K) Each dot represents an individual mouse. Error bars represent mean and SD. *p < 0.05; **p < 0.01; ***p < 0.001 (Student’s t test).
(L) Tumor growth over time following subcutaneous injection of 1 × 106 MC38 Rab27a null cells followed by tail vein exosomes derived from MC38 WT and MC38 Pd-l1 null cells grown in vitro. MC38 Rab27a null treated with WT versus Pd-l1 null exosomes, p < 0.01 (two-way ANOVA test).(M) Survival curve following injection of cells as in (L). MC38 Rab27a null tumors treated with WT versus Pd-l1 null exosomes, p < 0.01 (log rank test).
(L and M) Error bars represent SEM.