Selective Internal Radiation Therapy (SIRT) Promotes the Recruitment of Tumor-Infiltrating Lymphocytes and Enhances Cytotoxic Activity in Hepatocellular Carcinoma

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. Legal entity responsible for the study: Vincent Donckier Funding: None Disclosure: All authors have declared no conflicts of interest.