Figure 7.
TIGIT blockade promotes myeloma control after SCT. MM-bearing recipients were transplanted as previously described with BM+T grafts from B6 donors. Recipients were treated immediately after transplant with 100 μg anti-TIGIT or cIg per mouse twice a week for 6 weeks. (A) Tumor burden and survival of anti-TIGIT (maroon)– or cIg (gray)–treated mice (n = 19 combined from 3 experiments). Survival was analyzed using a log-rank test, and M-bands were modeled as described. (B-K) MM-bearing recipients were sacrificed 6 weeks after transplant after completion of treatment, and BM and spleen were harvested and analyzed using flow cytometry. FACS plots and histograms are representative. (B) Myeloma (CD19−CD155hi) and (C) CD8+ and CD4+ T-cell numbers in BM. (D) Histogram and frequency of DNAM-1+CD8+ T cells in BM. (E) FACS plot and frequency of TIM-3 and PD-1 expression on CD8+ T cells in the BM. (F) Histogram and geometric mean fluorescence intensity (GMFI) of Eomes expression in BM CD8+ T cells. (G-H) Whole BM was stimulated and IFN-γ and CD107a production was measured by intracellular staining. (G) Histogram and number of IFN-γ+ CD8+ and CD4+ T cells in cIg- and anti-TIGIT–treated mice, and (H) correlation of IFN-γ+ (n = 18 from 3 experiments) and CD107a+ (n = 13 from 2 experiments) CD8+ T-cell number with myeloma cell number in anti-TIGIT–treated mice. (I) Frequency of CD11chiCD64− cells within IL-10-GFP+ myeloid cells in the BM (n = 7-10 from 2 experiments). (J) FACS plots showing CD62L and CD44 expression, and graph showing frequency of TCM (CD44+CD62L+) and TEFF/EM (CD44+CD62L−) CD8+ T cells in the BM. (K) Histogram and graph of CD122 GMFI on CD122+CD8+TCM cells in the BM. In panels B-E, G, and J, n = 14-18 combined from 3 experiments; in panels F and K, n = 9-12 combined from 2 experiments. Data represent mean ± SEM. *P < .05, **P < .01, ***P < .001 (Mann-Whitney U test).

TIGIT blockade promotes myeloma control after SCT. MM-bearing recipients were transplanted as previously described with BM+T grafts from B6 donors. Recipients were treated immediately after transplant with 100 μg anti-TIGIT or cIg per mouse twice a week for 6 weeks. (A) Tumor burden and survival of anti-TIGIT (maroon)– or cIg (gray)–treated mice (n = 19 combined from 3 experiments). Survival was analyzed using a log-rank test, and M-bands were modeled as described. (B-K) MM-bearing recipients were sacrificed 6 weeks after transplant after completion of treatment, and BM and spleen were harvested and analyzed using flow cytometry. FACS plots and histograms are representative. (B) Myeloma (CD19CD155hi) and (C) CD8+ and CD4+ T-cell numbers in BM. (D) Histogram and frequency of DNAM-1+CD8+ T cells in BM. (E) FACS plot and frequency of TIM-3 and PD-1 expression on CD8+ T cells in the BM. (F) Histogram and geometric mean fluorescence intensity (GMFI) of Eomes expression in BM CD8+ T cells. (G-H) Whole BM was stimulated and IFN-γ and CD107a production was measured by intracellular staining. (G) Histogram and number of IFN-γ+ CD8+ and CD4+ T cells in cIg- and anti-TIGIT–treated mice, and (H) correlation of IFN-γ+ (n = 18 from 3 experiments) and CD107a+ (n = 13 from 2 experiments) CD8+ T-cell number with myeloma cell number in anti-TIGIT–treated mice. (I) Frequency of CD11chiCD64 cells within IL-10-GFP+ myeloid cells in the BM (n = 7-10 from 2 experiments). (J) FACS plots showing CD62L and CD44 expression, and graph showing frequency of TCM (CD44+CD62L+) and TEFF/EM (CD44+CD62L) CD8+ T cells in the BM. (K) Histogram and graph of CD122 GMFI on CD122+CD8+TCM cells in the BM. In panels B-E, G, and J, n = 14-18 combined from 3 experiments; in panels F and K, n = 9-12 combined from 2 experiments. Data represent mean ± SEM. *P < .05, **P < .01, ***P < .001 (Mann-Whitney U test).

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