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. 2020 Dec 30;24(1):102016. doi: 10.1016/j.isci.2020.102016

Figure 4.

Figure 4

Adoptive transfer of SASP-boosted therapy-induced senescent cells sensitizes ovarian tumor to anti-PD-1 treatment

(A) Schematics of experimental design. GFP-expressing UPK10 cells were orthotopically transplanted into the mouse bursa for two weeks to allow for tumor formation. The indicated control or sorted senescent UPK10 cells ex vivo induced by cisplatin, irinotecan or a combination of cisplatin and irinotecan were i.p. injected on day 15 and 22 and followed with anti-PD-1 antibody treatment on day 16, 19, 23 and 26. In addition, transfer of DMAXX ex vivo treated UPK10 cells were included as a control. Note that sorted non-senescent cells were used as control cells.

(B) At the end of two weeks of treatment, immunofluorescent staining revealed infiltration of injected non-senescent and senescent UPK10 cells (GFP and mCherry double positive) into the pre-established orthotopic tumors (only GFP-positive).

(C) Outline of experimental groups into which mice were randomized. Please note that control cells are sorted non-senescent cells.

(D and E) At the end of two weeks of treatment, reproductive tracts with tumors from the indicated treatment groups were dissected (D) and tumor weights were measured as a surrogate for tumor burden (E). (n = 5 biologically independent mice per group).

(F) After stopping the treatment, the mice from the indicated groups were followed for survival. Shown are the Kaplan–Meier survival curves of mice from the indicated treatment groups (n = 5 biologically independent mice per group).

(G) Fold changes in percentage of CD69+/CD8+ T cells in CD8+ T cell population and CD11b+ dendritic cells in dendritic cell population (normalized by tumor weight) were determined in tumors dissected from the indicated treatment groups (n = 5 biologically independent mice per group).

Data represent mean ± SEM. Scale bar = 200 μm in 4B. P-values were calculated using two-tailed t test in 4E, log-rank (Mantel–Cox) test in 4F, and multiple t test in 4G. n.s.: not significant. See also Figure S4.