Immunotherapeutic response score to predict prognosis for unresectable hepatocellular carcinoma with immune checkpoint inhibitors-based conversion treatment.

e16254 Background: Immune checkpoint inhibitor (ICI)-based conversion therapy is increasingly utilized for patients with initially unresectable hepatocellular carcinoma (HCC). However, Immune-related pathologic response (irPR) features in post-NAT HCC resection specimens and their clinical significance remain poorly understood. Methods: This study included 201 HCC patients who received ICIs-based conversion therapy and followed by curative resection. The irPR features and their clinical significance were explored, and immunotherapeutic response score (ITRS) was then developed including those irPR features are significant or showing a trend (P < 0.2) in correlation with overall survival (OS) or recurrence-free survival（RFS）. Kaplan-Meier and Cox regression analyses were performed to assess the relationship between ITRS and RFS as well as OS. Results: Assessment of Histological Samples Hematoxylin and eosin-stained (HE) slides of all cases were retrieved, scanned and digitalized. The archival slides from all cases were evaluated by two experienced histopathologists for the irPR features, who were blind to the follow-up data. Tumor immune infiltration density was evaluated as follows: Tumor infiltrating lymphocytes (TILs) were examined across the entire tumor area under low power microscopic field and the densest TIL area was selected. Lymphoid aggregates, tertiary lymphoid structures, neovascularization, foamy macrophages, giant cells, neutrophils and necrosis are scored based on the quantitative immune-related pathologic response criteria (irPRC). Then, Four irPR features (tumor infiltrating lymphocyte, lymphoid aggregate, foamy macrophage and neutrophil) were included in ITRS construction. A binary ITRS scheme was developed, wherein patients with ITRS 0-1 were classified into the ITRS-low group and ITRS 2-4 were classified into the ITRS-high group. ITRS-high group exhibited significantly worse OS (HR: 1.97, 95% CI: 1.09-3.55, p = 0.025) and RFS (HR: 1.61, 95% CI: 1.10-2.35, p = 0.015) in Kaplan-Meier analysis. Conclusions: This study proposed an irPR features-based ITRS scheme that significantly predicts OS and RFS in HCC patients receiving ICI-based conversion therapy. The ITRS is feasible for implementation in routine diagnostic pathology practice and offers novel insights into resistance mechanisms associated with immunotherapy. Further validation in future prospective multicenter clinical trials is warranted.