Figure 12.

Nivolumab therapy reduces the frequency of exhausted CD4⁺T cells in TILs and increases the frequency of activated CD4⁺and CD8⁺TILs producing IFN-γ. (A) tSNE map of CD4⁺ T cells infiltrating the tumor in samples before treatment (purple dots) and on-treatment with nivolumab (yellow dots). (B) tSNE map colored by clusters in CD4⁺ TILs. (C) Box plots showing the frequency CD4⁺ TIL clusters before and on nivolumab therapy. (D) Heatmap of the CD4⁺ TIL clusters changed after nivolumab therapy. The heatmap shows the normalized expression of the panel markers. The color scale indicates the relative expression levels. (E) tSNE map of CD8⁺ T cells infiltrating the tumor samples before treatment (purple dots) and on-treatment with nivolumab (yellow dots). (F) tSNE map colored by clusters of CD8⁺ TILs. (G) Box plots showing the frequency of CD8⁺ TIL clusters before and on nivolumab therapy. (H) Heatmap of the CD8⁺ TIL clusters changed after nivolumab therapy. The heatmap shows the normalized expression of the panel markers. The color scale indicates the relative expression levels. *P ≤ .05 and **P ≤ .001, Wilcoxon signed-rank test, adjusted with the Benjamini and Hochberg method. ns, not significant.