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. Author manuscript; available in PMC: 2017 Jul 17.
Published in final edited form as: Cell. 2016 Dec 1;167(6):1525–1539.e17. doi: 10.1016/j.cell.2016.11.005

Figure 4. LATS1/2 Deletion in Tumors Stimulates Host Adaptive Immunity and Enhances Tumor Vaccine Efficacy.

Figure 4

(A) WT or LATS1/2 dKO B16-OVA melanoma cells were injected into C57BL/6 mice, and tumor growth was monitored after the indicated times (left panel). For co-injection experiments, WT and LATS1/2 dKO cells were injected into opposite flanks in the same mouse (right panel). “WT [with LATS1/2 dKO(#1)]” (blue line) indicates WT tumor growth, and “LATS1/2 dKO(#1) [with WT]” (yellow line) indicates LATS1/2 dKO tumor growth, in the co-injected mice. Data are presented as means ± SEM; n = 8 tumors for WT or LATS1/2 dKO group, n = 6 tumors for each co-injected group. The p value was determined using two-way ANOVA test, comparing the “WT [with LATS1/2 dKO(#1)]” group to the WT group. ***p < 0.001.

(B and C) In (B), C57BL/6 mice were immunized intradermally at the base of the tail with equal numbers of irradiated WT or LATS1/2 dKO B16-OVA cells (or PBS control). 12 days after immunization, mice were challenged with WT B16-OVA melanoma, and tumor growth was monitored after the indicated times. Data are presented as means ± SEM; n = 8 tumors for each group. (C) Kaplan-Meier tumor-free survival curves for mice immunized and challenged as in (B) are shown (n = 12 mice for each group). The survival curve of C57BL/6 mice challenged with WT B16-OVA melanoma without vaccination in Figure 2C is also shown in light gray for reference. A schematic representation of vaccination experiment with irradiated-tumor cells is shown in the lower panel. The p value was determined using a two-way ANOVA test (B) or a log-rank test (C), comparing the WT-immunized group [WT / WT] to the LATS1/2 dKO-immunized group [LATS1/2 dKO(#1) / WT]. ***p < 0.001.

(D) C3H/HeOu mice were first injected with non-irradiated LATS1/2 dKO SCC7 cells. 60 days after the initial injection, mice designated tumor-free were re-challenged with WT SCC7 cells, and tumor growth was monitored [LATS1/2 dKO(#1) / WT]. The tumor growth curve of WT SCC7 injected into naive C3H/HeOu mice in Figure 2D is also shown in light gray for reference (WT). Data are presented as means ± SEM; n = 8 tumors for each group. ***p < 0.001, two-way ANOVA test. A schematic representation of the rechallenge experiment is shown in the lower panel.

(E) WT or LATS1/2 dKO B16-OVA cells were transplanted into Rag-1 knockout (KO) mice that lack mature B and T lymphocytes. Tumor growth was monitored after the indicated times. Data are presented as means ± SEM; n = 8 tumors for each group. ns, not significant (p > 0.05, two-way ANOVA test).

(F) Kaplan-Meier tumor-free survival curves for mice transplanted as in (E) are shown (n = 10 mice for each group). ns, not significant (p > 0.05, log-rank test).

(G) WT and LATS1/2 dKO B16-OVA melanoma cells were injected into opposite flanks in the same Rag-1 KO mouse. Data are presented as means ± SEM; n = 6 tumors for each group. The tumor growth curves shown in (E) are shown in a lighter color for reference. The p value was determined using a two-way ANOVA test, comparing the “WT [with LATS1/2 dKO(#1)]” group to the WT group. ns, not significant (p > 0.05).