Journal: Journal for Immunotherapy of Cancer
Article Title: Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control
doi: 10.1136/jitc-2024-009129
Figure Lengend Snippet: Early vaccination prevents liver tumor progression in AST;Cre-ER T2 mice. (A) Scheme: Early AST;Cre-ER T2 mice (42 days) were adoptively transferred with TCR TAG and left untreated (Φ) or the following day, immunized with empty LM (LMΦ) or LM expressing the TAG antigen (LM TAG ). One cohort (survival analysis) was followed to humane endpoint and the second (pre-endpoint analysis) analyzed at age 100 days prior to tumor endpoint. The † and numbers indicate the number of mice in the long-term cohort who reached humane endpoint and were euthanized. ( B ) Kaplan-Meier curve showing survival of mice in each group with n=5–6/treatment group. *p<0.05, **p<0.01 (log rank (Mantel-Cox) test). The ‡ indicates a mouse euthanized for endpoint of severe dermatitis, whereas all other mice were euthanized due to advanced liver tumors. ( C–F ) Cohort as in A was euthanized and analyzed at age 100 days prior to tumor endpoint. ( C ) Left, TCR TAG TNFα and IFNγ production after 4 hours ex vivo TAG peptide stimulation. Right, percentage of TCR TAG positive for IFNγ and TNFα/IFNγ. Each symbol represents an individual mouse with n=6–7/group. **p<0.01, ***p<0.001, ****p<0.0001 (one-way ANOVA with post hoc Tukey test). ( D ) Number of TCR TAG in spleen and livers. Each symbol represents an individual mouse with n=7–9/group. *p<0.05, ***p<0.001 (one-way ANOVA with post hoc Tukey test). ( E ) Left, histograms of TCR TAG PD1 expression. Right, percentage of PD1+TCR TAG with positive gate set to exclude naive TCR TAG (gray). Each symbol represents an individual mouse with n=2 for naive and n=7–9 for other groups. **p<0.01, ***p<0.001, ****p<0.0001 (one-way ANOVA with post hoc Tukey test). ( F ) Left, TCF1 and TOX expression in TCR TAG . Right, percentage of TCF1+TOX and TCF1-TOX+TCR TAG . Each symbol represents an individual mouse with n=8–9/group. *p<0.05, **p<0.01, ***p<0.001 (one-way ANOVA with post hoc Tukey test). C–F shows samples pooled from two independent experiments. ( G ) Early AST;Cre-ERT2 mice (42 days) were adoptively transferred with TCR TAG and immunized with LM TAG 7 days later (early LM TAG ) or 60 days later (at age 110 days) (late LM TAG ). Kaplan-Meier curve showing survival of mice in each group with n=5–8/treatment group. **p<0.01 (log rank (Mantel-Cox) test). ANOVA, analysis of variance; LM, Listeria monocytogenes.
Article Snippet: LM ΔactA ΔinlB expressing Tag-I epitope (SAINNYAQKL, SV40 large T antigen 206–215 ) (LM TAG ), or without exogenous antigens (LMΦ), were generated by Aduro Biotech and stored at −80°C.
Techniques: Expressing, Ex Vivo
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