Fig. 5
After pembrolizumab infusion, in association with nintedanib treatment, circulating and tumor microenvironment changes were associated with distinct clinical outcomes. A Plasma levels of soluble TNF increased in patients without DCB between C1D1 (0.7 pg/mL [range: 0.4–1.1]) and C2D1 (1.8 pg/mL [range: 0.8–3.4]) (Paired Wilcoxon signed rank test; p = 0.015) instead of in patients with DCB. B Plasma rate of IL6, IL8 and IL27 were significantly higher at C2D1 in patients without DCB (9.6 pg/mL [range: 3.5–22.4], 10.8 pg/mL [range: 5.8–16.7] and 380.9 pg/mL [range: 181.8–845.2], respectively) than those with DCB (1.7 pg/mL [range: 0.6–4.14], 4.9 pg/mL [range: 1.7–6.8] and 163.9 pg/mL [range: 56.6–247.4], respectively) (non-parametric Wilcoxon rank sum test; p = 0.01, p = 0.01 and p = 0.03, respectively). C Percentage of PDL1+ tumor cells, ratio of CD3+ per CD163+ cells and FOXP3+ cells density in biopsies of patients with DCB (41.8% [range: 2–90], 1.9 [range: 0.8–3] and 221/mm2 [range: 116–320], respectively) was higher than patients without DCB (3% [range: 0–20], 0.5 [range: 0.06–1.4] and 49/mm2 [range: 1–158], respectively) at C2D1 (non-parametric Wilcoxon rank sum test; p = 0.009, p = 0.047 and p = 0.03, respectively). D Illustration of increased expression of PDL1 at tumor cell’s surface, CD3+ and FOXP3+ T cells infiltration in tumor microenvironment observed with IHC analysis (patient #3). Abbreviations: PD = Progressive disease; SD = Stable disease; PR = Partial response; Ninte. = nintedanib; DCB = Durable clinical benefit; C1 = Cycle 1; TNF = Tumor Necrosis Factor