The PD-L1/PD-1 axis expression on tumor-infiltrating immune cells and tumor cells in pediatric rhabdomyosarcoma

Background: Activation of immune checkpoints, e.g. PD-1/PD-L1 axis, in cancer microenvironment, enables evasion of host anti-cancer immune response and drives tumor progression. To date, there have been only a few studies analyzing PD-1/PD-L1 expression in pediatric malignancies. Aim: In the current study, we aimed to assess PD-Ll and PD-1 expression in pediatric rhabdomyosarcoma (RMS) and to investigate their clinicopathological associations. Materials and methods: The study enrolled 31 children with RMS. Tissue microarrays with representative tumor tissue samples were stained with anti-PD-1 NAT105 clone (Ventana, Roche) and two different antibodies against PD-Ll: SP142 (Ventana, Roche) and 22C3 (DAKO). Adequate positive controls were applied. Their expression was assessed in tumor-associated immune cells (TAICs) and in the tumor cells separately. Results: We did not detect any positive PD-Ll staining in analyzed tumors using SP142 antibody; however, in 11 cases (35.48%) its expression was revealed by means of 22C3 clone. The staining was restricted to TAICs in all cases, which no reaction in tumor cells. The 5-year relapse free survival (RFS) rate was significantly higher in PD-L1 positive cases (61.5% vs 25.0%, p = 0.024), but it most likely results from more frequent PD-Ll expression in low-stage RMS. PD-1 expression on TAICs was detected in 7 cases and did not influence the prognosis. Conclusions: We found that PD-Ll expression on TAICs, as detected with the use of 22C3 clone but not SP142 antibody, tends to be associated with low-stage RMS in children. PD-1 expression on TAICs in RMS is neither associated with distinct clinical course nor with clinicopathological features.