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. 2020 Nov 6;8(2):e001355. doi: 10.1136/jitc-2020-001355

Figure 7.

Figure 7

Combined IL-15 stimulation and TIGIT blockade augments killing of sarcomas in vitro when target expression of TIGIT ligands is high. Analysis of the TCGA-SARC database by Kaplan-Meier analysis shows a significant survival advantage in tumors with a (A) high NK signature (p=0.0003), (B) high CD8 signature (p=0.03), but independent of (C) TIGIT expression (p=0.17). (D) TIGIT expression within STS tumors has a strong positive correlation with NK signature (r=0.82, p<0.0001) and CD8 signature (r=0.90, p<0.0001). (E) Low expression of the primary TIGIT ligand CD155 was associated with improved overall survival by Kaplan-Meier analysis of the TCGA-SARC database (p=0.04). (F) Expression of TIGIT ligand CD155 on sarcoma cell lines A673 (red) and SK-LMS (blue) compared with FMO staining. (G) Increased cytotoxicity of CFSE-labeled target cells A673 (left) and SK-LMS (right) following 4-hour incubation with in vitro IL-15-preactivated PBMCs from a patient with sarcoma in the presence anti-TIGIT 10 ug/mL (red) compared with IgG control 10 ug/mL (blue) at low and high E:T ratios. Increased expression of degranulation marker CD107a on NK cells from IL-15-preactivated PBMCs following 4-hour incubation with sarcoma cell lines shown by (H) representative flow cytometry against A673 cells, and (I) quantified per cent expression against A673 and SK-LMS cell lines in a 5:1 E:T ratio. These experiments were repeated independently in two patients with STS with representative data shown. P value determined using Student’s t-test using n=3–4 technical replicates. FMO, Fluorescence Minus One; IL, interleukin; PBMCs, peripheral blood mononuclear cells; STS, soft tissue sarcoma; TCGA, The Cancer Genome Atlas.