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case_images: Clinical, pathological, and genetical characteristics of the patient before treatment. (A) Representative magnetic resonance imaging of the lesions before treatment. (B) Representative pathological images of the biopsy tumor tissue before treatment. (C) Abundance of gene mutation of the biopsy tumor tissue before treatment. (D) Tumor mutation burden distribution in liver cancer patients sequenced in Geneplus. (E) Coverage comparison of HLA-A supertype, HLA-B supertype, and HLA-C supertype.
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case_images: Magnetic resonance images revealed a huge tumor (10*7 cm) in the right lobe of the liver with multiple intrahepatic metastases, and with tumor thrombosis growing into the right portal vein ( Figure 1A ). Pathologic analysis of tumor tissue confirmed the diagnosis of HCC, as indicated by Glypican3(+), CK19(-), and CK7(-), and showed poor differentiation (Edmondson grade III), and proliferative phenotype (Ki-67 Li: 50%-60%) ( Figure 1B ). Table 1 ) next-generation sequencing (GenePlus OncoD, Geneplus, Beijing) was used to analyze the gene feature of tumor tissue. The results showed that 20 genes mutated or had copy number variation in tumor tissues ( Figure 1C ,  Supplementary Tables 2, 3 ). Tumor mutational burden (TMB) was calculated as 19.2 Muts/Mb and was classified as high TMB ( Figure 1D ). We then estimated the loss of heterozygosity (LOH) of human leukocyte antigen (HLA) class I at the somatic level and found that this patient harbored subclonal LOH of HLA-A and HLA-C supertype while maintaining HLA-B supertype heterozygosity ( Figure 1E ). Moreover, CD8 staining showed scattered infiltration of CD8+ T cells in the HCC tissue ( Figure 1B ), and PD-L1 staining revealed a tumor proportion score (TPS) of 5% and a combined proportion score (CPS) of 8.
case_images: Clinical course and radiologic images throughout the conversion therapy. (A) Clinical course and magnetic resonance imaging changes of the lesion throughout the conversion therapy. (B) Tumor biomarker AFP and PIVKA-II changes throughout the conversion therapy. (C) 3D reconstruction model of the liver and future liver remnant volume changes throughout the conversion therapy.
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case_images: Table 1 ) next-generation sequencing (GenePlus OncoD, Geneplus, Beijing) was used to analyze the gene feature of tumor tissue. The results showed that 20 genes mutated or had copy number variation in tumor tissues ( Figure 1C ,  Supplementary Tables 2, 3 ). HCC due to its low FLV (as shown in  Figure 2C , the initial FLV was 351.03 cm3 and the standard liver volume was estimated as 1,049.86 cm3. The FLV estimated standard liver volume ratio (FLV/ESLV) was 33.4%), as well as its staging of BCLC stage C, CNLC stage At the first follow-up in July 2022, blood tests revealed significant decrease in serum levels of AFP (9164 ng/mL), PIVKA-II (967.41 mAu/mL), and HBV-DNA < 1x102 IU/mL ( Figure 2B ). Tumors (mRECIST) criteria ( Figure 2A ). The time to response is around 6 weeks. In September 2022, the patient had undergone three cycles of combined therapy, and radiologic measurements of lesions revealed PR (mRECIST criteria), with the tumor and PVTT shrinking significantly ( Figure 2A ). Child-Pugh grade A ( Figure 2B ). Considering that all HCC lesions of this patient located in hemi-liver and shrunk after combined therapy, we evaluated the resectability by measuring FLV and indocyanine green retention test after 15 min (ICG-R15). FLV was insufficient even after tumor shrinkage (as shown in  Figure 2C , the FLV was 404 cm3 and the standard liver volume was estimated as 1,049.86 cm3. FLV/ESLV was 38.4%). At the follow-up of 9 weeks (November 2022) after combined DEB-TACE and PVE, the tumor continued to shrink and the future liver remnant volume increased to 670.65 cm3, which occupied 63.8% of the standard liver volume, with the atrophy of the right hemi-liver ( Figures 2B, C ).
case_images: Intraoperative and postoperative clinical course of the case. (A) The image of the resected specimen. (B-D) Representative pathological images of the resected tumor. (E-I). Postoperative changes of biochemical tests of liver function. (J) Representative computed tomography images of the liver remnant after the operation.
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case_images: Table 1 ) next-generation sequencing (GenePlus OncoD, Geneplus, Beijing) was used to analyze the gene feature of tumor tissue. The results showed that 20 genes mutated or had copy number variation in tumor tissues ( Figure 1C ,  Supplementary Tables 2, 3 ). FLV was insufficient even after tumor shrinkage (as shown in  Figure 2C , the FLV was 404 cm3 and the standard liver volume was estimated as 1,049.86 cm3. FLV/ESLV was 38.4%). HCC. He underwent right hemi-hepatectomy after discontinuation of lenvatinib for 3 weeks in December 2022 ( Figure 3A ). The pathological examination showed necrosis of a massive HCC (major pathological response, MPR) with no tumor cells observed on the resection margins ( Figure 3B ). The immunohistochemical analysis of resected tissue showed CD8 (scattered lymphocyte+) and Ki-67 (Li: 10%) ( Figures 3C, D ). He achieved a textbook outcome after hepatectomy and was discharged 14 days after surgery ( Figures 3E-J ).
case_images: Imaging examinations and tumor biomarker changes during the follow-up. (A) Representative ultrasound images or computed tomography images during the follow-up. (B) Tumor biomarker AFP and PIVKA-II changes during the follow-up.
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case_images: There was no clinical evidence of recurrence at 9 months after the resection, and the AFP levels remained within the normal limit ( Figure 4 ).