Fig. 5: LSD1 inhibitor-primed OT1 cells show reduced exhaustion and enhanced antitumor efficacy. | Nature Communications

Fig. 5: LSD1 inhibitor-primed OT1 cells show reduced exhaustion and enhanced antitumor efficacy.

From: Priming with LSD1 inhibitors promotes the persistence and antitumor effect of adoptively transferred T cells

Fig. 5

Tumor growth and survival curves of mice subcutaneously inoculated with B16-OVA (a, b) or Yumm1.7-OVA (c, d) tumor cells and transferred with 1 million GSK-, ORY1001- or Veh-primed OT1 cells, or PBS as indicated (n = 6 mice per group). e Abundance of transferred CD45.2 OT1 cells in B16-OVA tumors, detected by flow cytometry on day 5 post transfer (n = 3 mice per group). Flow cytometry analysis of PD-1 (f), CD39 (g), and TIM-3 (h) expression in B16-OVA tumor-infiltrating OT1 cells (TILs) on day 5 post transfer (n = 3 mice per group). i Percentages of CD44+CD62L+ cells in OT1 TILs (n = 3 mice per group). Tumor growth (j) and survival curves (k) of B16-OVA tumor-bearing mice transferred with 1 million GSK- or Veh-primed OT1 cells or PBS, and injected with anti-PD1 or isotype control as indicated (n = 6 mice per group). l Tumor growth curves of B16-OVA tumor-bearing mice transferred with PBS or Rosa26Cre-ERT2Lsd1f/f OT1 cells with vehicle or 4-OHT treatment during the 2-day activation period (4-OHT at Activation) or the 3-day expansion period (4-OHT at Expansion) (n = 5–6 mice per group as indicated). m Tumor growth curves of B16-OVA tumor-bearing mice transferred with 5 million OT1 cells primed with GSK for different time durations (n = 6–8 mice per group as indicated). n Flow cytometry of PD-1, SLAMF6, and CD62L in OT1 cells treated with GSK for the indicated times during in vitro activation and expansion and analyzed on day 6 (n = 3). o CETSA assay detecting soluble LSD1 in activated CD8+ T cells collected after treatment with 0.5 μM GSK for the indicated hours and heated at 53 °C. p CETSA assay detecting soluble LSD1 in activated CD8+ T cells treated with 0.5 μM GSK for the indicated time durations and collected after 6 days of total culture. Data are representative of three (a, b) or two (c–l, n–p) independent experiments and are presented as mean ± SEM (a–m) or mean ± SD (n). Statistical significance was determined by two-sided unpaired t-test (e–i, n), two-way ANOVA (a, c, j, l, m), or log-rank test (b, d, k). Source data are provided as a Source Data file.

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