Anna Gabrych1, Rafał Pęksa2, Michał Kunc2, Małgorzata Krawczyk1, Ewa Izycka-Swieszewska3, Wojciech Biernat2, Ewa Bień4. 1. Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland. 2. Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland. 3. Department of Pathology and Neuropathology, Medical University of Gdańsk, Gdańsk, Poland. 4. Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: ebien@gumed.edu.pl.
Abstract
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-L1 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-L1: 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-L1 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-L1 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-L1 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.
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-L1 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-L1: 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-L1 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-L1 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-L1 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.
Authors: Łukasz Zapała; Michał Kunc; Sumit Sharma; Rafał Pęksa; Marta Popęda; Wojciech Biernat; Piotr Radziszewski Journal: J Cancer Res Clin Oncol Date: 2022-08-30 Impact factor: 4.322