Figure 2. Th1 cells are essential for anti-tumor immunity and long-term survival in glioblastoma.
(A) Uniform manifold approximation and projection (UMAP) of single-cell RNA-seq from IgG and αCTLA-4 treated 005 tumors. (B) The highly expanded clonotypes was displayed overlaid with the UMAP in each subset from A. (C) Shared clonotype analysis in non-Treg CD4+ T cells between IgG vs. αCTLA-4 treatment by alluvial clonotypes. (D) Feature plot showed Ifng and Tbx21 in the different clusters between IgG vs. αCTLA-4 as defined in A. (E) Heatmap of expression dynamics of transcription factors, cytokines and others enriched in the different clusters between IgG vs. αCTLA-4. (F) The expression of IFNγ, TNF, IL-2 in CD4+ T cells from harvested brains. (G) Tbx21+/+ or Tbx21−/− mice were implanted 005 GSCs and with indicated treatment. Median survival of IgG (53 days; n = 5) was compared with αCTLA-4 (77.5 days; n = 6, p = 0.00369). Median survival of Tbx21−/− (37 days, n=5) was compared with Tbx21−/− treated with αCTLA-4 (33 days; n = 7, p = 0.85176). Similarly, comparison of αCTLA-4 treatment of wild-type B6 mice with that of Tbx21−/− (33 days; n = 7, p = 0.00036), as well as the corresponding comparison in αCTLA-4 combined with αIFNγ (43 days; n = 9, p = 0.00045), were done by log-rank analysis. All the results were pooled from or representative of 2–4 experiments with n = 3–5 mice / group (A-E), n = 4–11 mice / group (F).