Differential Organ-Specific Tumor Response to Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Abstract

<b><i>Background and Aims:</i></b> Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs. <b><i>Methods:</i></b> We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites. <b><i>Results:</i></b> Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (<i>p</i> = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (<i>p</i> = 0.005). <b><i>Conclusions:</i></b> The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.

Prognostic and immune regulating roles of YIF1B in Pan-Cancer: a potential target for both survival and therapy response evaluation

“…The link between expression of YIF1B and malignancy progression and recurrence in LIHC patients was consistent in different databases. Although much more information on the molecular role of YF1B in immune regulation is required to understand the strong correlation between YIG1B expression and LIHC, the liver is a highly metabolic organ with a different immune microenvironment, and more recent studies have described it as an immune suppressive organ [36,37]. In our results, YIF1B expression is highly related to immune cell infiltration in LIHC, as well as TMB, the MMR gene and methylation transferase expression.…”

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

“…In 90 patients with advanced malignancies (mostly melanoma and GI tumors) treated with CPIs in Phase I trials, the presence of liver metastasis was significantly associated with shorter OS, PFS, and lower rate of clinical benefit (204). In a retrospective review of 75 patients with advanced HCC, ORRs in the liver, lung, lymph node, and other intra-abdominal metastases were 22%, 41%, 26%, and 39%, respectively (207). Together, these clinical data suggest that hepatic metastases may be less responsive to CPIs than extrahepatic lesions.…”

Immune system‑associated genes increase malignant progression and can be used to predict clinical outcome in patients with hepatocellular carcinoma

“…However, the specific immune genetic changes in HCC have not been extensively studied, although one study found that the levels of immune cells infiltration, specifically by T-cells, cytotoxic cells, Th2 cells and macrophages, in HCC were associated with improved survival in patients based on n silico analysis, suggesting that the type of immune cells present in HCC tissues were different from the immune cell profile of the normal liver (15). As the liver is now considered to a 'immune associated organ', the presence of immune cells in HCC should be taken into consideration as a leading factor for predicting prognosis following resection, and should not be restricted to specific types of immune cells (16)(17)(18).…”