26 research outputs found
Interaction between baseline HBV loads and the prognosis of patients with HCC receiving anti-PD-1 in combination with antiangiogenic therapy undergoing concurrent TAF prophylaxis
Key points Baseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with antiangiogenic therapy. Besides, PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment undergoing concurrent TAF prophylaxis
Transarterial chemoembolization with/without immune checkpoint inhibitors plus tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a single center, propensity score matching real-world study
Abstract Objectives To explore the efficacy and safety of Transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC). Methods 456 patients with HCC receiving either TACE in combination with ICIs and TKIs (combination group, n = 139) or TACE monotherapy (monotherapy group, n = 317) were included from Apr 2016 to Dec 2021 in this retrospective study. We employed propensity score matching (PSM), performed 1:2 optimal pair matching, to balance potential bias. Results The mean follow-up time is 24.7 months (95% CI 22.6–26.8) for matched patients as of March 2022. After matching, the combination group achieved longer OS and PFS (median OS:21.9 vs. 16.3 months, P = 0.022; median PFS: 8.3 vs. 5.1 months, P < 0.0001) than TACE monotherapy group. The combination group had better objective response rate (ORR) and disease control rate (DCR) (ORR: 52.5% vs. 32.8%, P < 0.001; DCR: 82.7% vs. 59.6%, P < 0.001). Subgroup analysis showed that patients who received “TKIs + ICIs” after the first TACE procedure (after TACE group) achieved longer OS than those before the first TACE procedure (before TACE group) (26.8 vs. 19.2 months, P = 0.011). Adverse events were consistent with previous studies of TACE-related trials. Conclusions TACE plus TKIs and ICIs appeared to deliver longer PFS and OS in HCC patients than TACE monotherapy. “TKIs + ICIs” co-treatment within 3 months after the first TACE procedure might be a better medication strategy
Elevated Pretherapy Serum IL17 in Primary Hepatocellular Carcinoma Patients Correlate to Increased Risk of Early Recurrence after Curative Hepatectomy
<div><h3>Background and Aims</h3><p>Primary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.</p> <h3>Methods</h3><p>A cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated <em>in vitro</em> from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.</p> <h3>Results</h3><p>All the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (≥0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34–4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (<em>P</em> = 0.009) or without any (<em>P<</em>0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNFα was included.</p> <h3>Conclusion</h3><p>Both tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients.</p> </div
Intracellular IL17 staining in PBMCs and IHL of HCC patients.
<p>A: IL17 staining in PBMCs or IHL isolated from one representative of 9 independent HCC patients stimulated with anti-human-CD3 and CD28 (CD3+CD28). As parallel, IHL in 3 of the HCC patients were stimulated with PMA and Ionomycin (PMA+ION) were used to confirm the presence of IL17-producing T cells. Analysis was based on CD3<sup>+</sup> gating (gating strategy is provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050035#pone.0050035.s002" target="_blank">Figure S2</a>). B: Percentage of IL-17<sup>+</sup> cells in the indicated cell populations. Each dot represents one of HCC patient. PBMCs: peripheral blood monoculear cells; IHL: intrahepatic lymphocytes. PMA: phorbol 12-myristate 13-acetate, ION: Ionomycin. **indicates <i>P<</i>0.001.</p
Effects of serum levels of IL17 and tumor size on HCC early recurrence (A,B,C) and overall survival of the patients (D,E,F).
<p>Kaplan-Meier estimate on HCC recurrence based on elevated serum levels of IL17 alone (A), on tumor size alone (B), and on combination of the two factors (C). Kaplan-Meier estimate patient overall survival based on elevated serum levels of IL17 alone (D), on tumor size alone (E), and on combination of the two factors (F).</p
Associations between the pretherapy serum levels of IL17 and IL10 and general clinicopathological factors in HCC patients.
*<p>Mann-Whitney U test.</p
Sensitivity and specificity of elevated pre-therapy serum IL17 and bigger tumor size in predicting HCC early recurrence and overall survival.
<p>Sensitivity and specificity of elevated pre-therapy serum IL17 and bigger tumor size in predicting HCC early recurrence and overall survival.</p
Proliferation of hepatocellular carcinoma cells in presence of activated IL17-producing T cells.
<p>A: Diagram of the co-culture experiments. B, C: The proliferation of HCC cells, QGY-7703 or Hep3B cell lines, was determined using a CCK8 reagents after being co-cultured with IL17-producing T cells for 48 h. PBMCs were isolated from the HCC patients and cultured with recombinant human IL-23 in the presence of plate-bound anti-human CD3 and anti-human CD28 for 7–10 days. IL17 production was confirmed by intracellular staining (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050035#pone.0050035.s003" target="_blank">Figure S3</a>). The proliferation of HCC cells (ctrl) containing anti-human CD3 and anti-CD28 antibodies in the medium but without adding cultured T cells in the upper chambers was used as control. All the antibodies used here were 5 µg/ml. Letter “c” represents isotype control. The upper chambers contained T cells were removed before CCK8 reagents were added. Triplicates were performed for each of the treatment. *: <i>P<</i>0.05. Data shown is representative one from 3 independent experiments.</p
Associations between HCC early recurrence and serum levels of IL17 and IL10, as well as some selected clinicopathological factors in HCC patients<sup>#</sup>.
#<p>The other clinicopathological factors on HCC early recurrence was presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050035#pone.0050035.s004" target="_blank">Table S1</a>.</p>a<p>HR: hazard ratio.</p>b<p>Adjusted for age, gender and the other factors included in this table.</p>*<p>
<i>P<0.05.</i></p
General information of 105 cases of HBV related HCC patients.
*<p>Barcelona Clinic Liver Cancer classification.</p