The immune system is believed to have an important role in solid tumor progression. The development of monoclonal antibodies targeting immune checkpoints, such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), have revolutionized the treatment of some cancers. Recent efforts have attempted to elucidate the relevance of the PD-1/PD-L1 pathway in gastrointestinal stromal tumors (GIST).
Formalin-fixed, paraffin-embedded specimens were obtained from resected GIST at Sunnybrook Health Sciences Centre between March 2008 and August 2015. PD-L1 analysis was based off a tissue microarray of the cases using the Roche Ventana SP263 antibody. Each case had 1mm cores taken from different areas of the tumor block. Normal controls used for PD-L1 were placenta and tonsil (epithelial and inflammatory). CD117 was assessed via immunohistochemistry in all tumor specimens.
Of twenty-nine patients who underwent surgical resection, eight had insufficient tumor tissue for analysis, and three cases were excluded due to CD117 negativity after preoperative imatinib treatment, leaving 18 patients for analysis. Three of these 18 cases were positive for PD-L1 expression: 2 patients with moderate PD-L1 staining in 85% of the stromal cells and 1 with weak staining in 15% of the stromal cells. Fifteen patients were negative for PD-L1 expression. Analysis of PD-L1 expression in tumor-infiltrating lymphocytes was not feasible due to the lack of inflammatory cells in tumor environment. The patients whose samples had significant PD-L1 expression had gastric primaries, with tumour size 5
In this cohort, PD-L1 may be a favorable prognostic biomarker. Further studies to examine the clinical benefit of immunotherapy in GIST patients with or without PD-L1 expression are warranted.
Clinical trial identification
Legal entity responsible for the study
Ana Beatriz Kinupe Abrahao
Glenita Mungcal GIST Research Award from the Life Raft Group Canada
All authors have declared no conflicts of interest.