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Quantitative Multiplexed Immune Profiling of Advanced Gastrointestinal Stromal Tumors (GISTs): Impact of tyrosine kinase inhibitors on immune environment

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Presenters

Changhoon Yoo

Citation

Annals of Oncology (2018) 29 (suppl_8): viii576-viii595. 10.1093/annonc/mdy299

Authors

C. Yoo1, S. Kim2, J. Kim3, Y. Ryu4, M. Ryu5, Y. Kang1

Author affiliations

  • 1 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 2 Department Of Convergence Medicine, Asan Institute for Life Sciences, 05505 - Seoul/KR
  • 3 Department Of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 4 Department Of Convergence Medicine, Asan Institute for Life Sciences, 138-736 - Seoul/KR
  • 5 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 05505 - Seoul/KR
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Resources

Background

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.

Methods

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.

Results

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).

Conclusions

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

Yoon-Koo Kang.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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