PMC9372450_01
Course of the patient's treatments. (A) Timelines of main treatments and changes in alpha-fetoprotein (AFP) levels during each period.(B) Representative imaging assessments during each period, including hepatic magnetic resonance (T2-weighted) and pulmonary computerized tomography (CT) in three different sections. Red arrows indicate the tumors.
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In February 2016, the patient was diagnosed with HCC in liver segments V and VI (6*5 cm) ( Figure 1B ) and underwent hepatectomy with R0 resection. Seven months later, the patient received trans-hepatic arterial chemotherapy and embolization (TACE) twice because of suspected tumor recurrence indicated by re-increased alpha-fetoprotein (AFP) levels ( Figure 1A ). In September 2017, imaging scans revealed multiple relapsed metastatic tumors in the lung but not in the liver ( Figure 1B ). April 2018 and was discontinued 3 weeks later due to an intolerable side effect of severe rash. After the cessation of sorafenib treatment, the patient's AFP level continued to increase ( Figure 1A ). The AFP level soon decreased to 19.0 g/L after three cycles of sintilimab and remained stable between 12.0 to 20 g/L from January 2019 to July 2019 ( Figure 1A ). The single remaining pulmonary nodule neither regressed nor progressed during 9 months of sintilimab treatment ( Figure 1B ). The imaging scans also showed no signs of recurrence in recent months ( Figure 1B ). T cells (Tregs) were only identified in the metastatic site while more T and B cells were found in the metastatic site compared to that in the primary tumor site. The infiltration of other immune cells such as macrophages, natural killer cells, and dendritic cells was comparable between these two sites ( Supplementary Figure S1 ).
Representative pathological sections of primary and recurrent tumors. (A) In the primary tumor in the liver, H&E staining and IHC showed infiltration of a few CD8-positive T cells and negative PD-L1 expression. (B) In the remaining tumor in the lung after sintilimab treatment, H&E staining and IHC showed infiltration of CD8-positive T cells in the mesenchymal area but not in the tumor and focal PD-L1 expression.
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We also performed pathological assessments to further show the heterogeneity between the primary site ( Figure 2A ) and the resected metastatic nodule ( Figure 2B ) after sintilimab treatment. The results showed that in the primary tumor site ( Figure 2A ), the tumor was composed of moderately differentiated HCC with a few infiltrated cytotoxic T cells and negative PD-L1 expression.