Role of immune microenvironment in gastrointestinal stromal tumours

Abstract

Aims The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment, including tumour‐infiltrating lymphocytes (TILs) and expression of programmed death‐ligand 1 ( PD ‐L1), indoleamine 2,3‐dioxygenase ( IDO ) and tryptophanyl‐ tRNA synthetase ( WARS ) in gastrointestinal stromal tumours ( GIST s) is largely unknown. Methods and results Tissue microarrays were constructed from pathology files, 1996–2016. Immunohistochemistry for PD ‐L1, IDO and WARS was correlated with tumour size, mitoses and outcomes. TILs expressing CD 3, CD 4, CD 8, FoxP3 and GBP 5 were counted. A total of 129 GIST s were analysed. Mean patient age was 62.5 years; 52.0% were male. Tumour location included 89 stomach (69.0%), 33 small bowel (25.6%) and seven other (5.4%). Mean tumour size was 5.6 cm; mean mitoses were 7.2 per 50 high‐power field. Nineteen patients (15.0%) developed disease progression, to abdominal wall ( n = 8), liver ( n = 6) and elsewhere ( n = 5). Median progression‐free survival was 56.6 months; five patients died of disease. PD ‐L1 was positive in 88 of 127 tumour samples (69.0%), 114 of 127 tumours were IDO ‐positive (89.8%) and 60 of 127 were positive for WARS (47.2%). PD ‐L1 was associated with increased size ( P = 0.01), necrosis ( P = 0.018) and mitoses ( P = 0.006). Disease progression was not associated with PD ‐L1 ( P = 0.44), IDO ( P = 0.14) or WARS ( P = 0.36) expression. PD ‐L1‐positive GIST s with CD 8 + or CD 3 + TIL s were significantly smaller than tumours with CD 8 + or CD 3 + TIL s. Conclusions PD ‐L1 expression was associated with increased size and mitoses. High CD 8 + or CD 3 + TIL counts were associated with decreased PD ‐L1/ IDO + GIST size. PD ‐L1 and IDO could be significant in GIST tumour biology, which invites consideration of immunotherapy as a potential treatment option.