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Selective internal radiation therapy (SIRT) promotes the recruitment of tumor-infiltrating lymphocytes and enhances cytotoxic activity in hepatocellular carcinoma (10PD)

Date

09 Dec 2017

Session

Poster Discussion session

Presenters

Ligia Craciun

Citation

Annals of Oncology (2017) 28 (suppl_11): xi3-xi5. 10.1093/annonc/mdx710

Authors

L. Craciun1, R. De Wind1, P. Demetter2, V. Lucidi3, S. Michiels4, S. Garaud5, C. Naveaux5, M. Gomez Galdon1, A. Hendlisz6, K. Willard Gallo5, P. Flamen7, D. Larsimont1, V. Donckier4

Author affiliations

  • 1 Pathology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
  • 2 Pathology, Hôpital Erasme, Université Libre de Bruxelles, 1070 - Brussels/BE
  • 3 Surgery, Hôpital Erasme, Université Libre de Bruxelles, 1070 - Brussels/BE
  • 4 Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
  • 5 Molecular Immunology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
  • 6 Digestive Oncology Clinic, Institute Jules Bordet, 1000 - Brussels/BE
  • 7 Nuclear Medicine, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
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Resources

Background

Intra-arterial therapies, including transarterial chemoembolization (TACE) and selective internal radiation therapy with 90Yttrium (SIRT), are effective locoregional treatments for hepatocellular carcinoma (HCC). High levels of tumor-infiltrating lymphocytes (TILs) are associated with a better prognosis in HCC. We hypothesized that TACE and SIRT may modify immunogenic tumor microenvironment. To analyze this question, we evaluated TILs in patients who underwent partial hepatectomy for HCC after preoperative TACE or SIRT and in patients operated without preoperative treatment (SURG).

Methods

Epidemiological, clinical and pathological data were analyzed in SIRT (n = 12), TACE (n = 16) and SURG (n = 32) groups. Sections for digital image analysis (DIA) were prepared from paraffin blocks. Immunohistochemistry stains were performed for CD3, CD4, CD8, CD20 and Granzyme B. The slides were scanned and analyzed with DIA Visiopharm software. After exclusion of the necrotic zones, TILs were quantified as percentages of positive cells/analyzed area.

Results

Baseline patient and tumor characteristics were similar in the 3 groups. Median times between SIRT or TACE and partial hepatectomy were not significantly different (16 versus 11 weeks). In resected HCC, preoperative SIRT significantly increased CD3+ TILs, including both CD4+ and CD8+ subpopulations, as compared to TACE and SURG groups. Preoperative TACE did not significantly affect TILs, neither for CD3+ nor for CD4+ or CD8+ subpopulations, as compared to the SURG group. CD20+ B lymphocyte infiltrates were similar in the 3 groups. Significantly increased expression of Granzyme B was demonstrated in SIRT patients while no modification of Granzyme B levels was observed between TACE and SURG patients.

Conclusions

In contrast with TACE, SIRT increases TILs levels and intratumor cytotoxic activity in HCC. These results suggest that local attraction/activation of effector T cells may contribute to the anti-tumor effect of SIRT, supporting the clinical development of therapeutic approaches combining SIRT and immunotherapy.

Clinical trial identification

Legal entity responsible for the study

Vincent Donckier

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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