Immune microenvironment of GISTs is largely unknown and there is no approved immunotherapeutic agent for the treatment of advanced GISTs. To investigate novel immunotherapeutic strategy in patients with GISTs, immune microenvironment was analyzed in this analysis.
In this study, 80 surgical specimens of GISTs from 65 patients in different clinical setting (TKI-naïve [n = 20], imatinib-progression [IM-PD, n = 30], and imatinib-progression and sunitinib-treated [IM-PD/SU-treated, n = 30]) were included. CD3, CD8, FoxP3, PD-L1, PD-1 and DOG-1 were simultaneously evaluated in one formalin-fixed paraffin-embedded tissue section using multiplexed immunohistochemistry (IHC) with computational image processing workflows for quantitative assessment.
IM-PD/SU-treated group showed increased FoxP3+CD3+/CD3+, PD-1+CD3+/CD3+, and PD-1+CD8+/CD3+ T cell ratios compared to TKI-naïve (p = 0.007, p = 0.004, and p = 0.007, respectively) and IM-PD (p = 0.008, p = 0.002, and p = 0.01, respectively) groups. PD-1 expression (>1%) on tumor cells (PD-1+DOG-1+/DOG-1+) were also higher in IM/PD-SU-treated group (10%) compared to TKI-naïve (0%) and IM-PD (3%) groups. There were no significant differences in immune microenvironment profiles between TKI-naïve and IM-PD groups (p > 0.05).
Anti-angiogenic agents may have immunomodulatory activity in advanced GISTs. Immune exhaustion phenotype (increased Treg, PD-1+ T cells and PD-1+ tumor cells) in IM-PD/SU-treated patients might indicate that this group is a potential candidate for future immunotherapy trials.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
All authors have declared no conflicts of interest.