Dataset Information

Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma.

ABSTRACT: Immune checkpoint inhibitors are effective for advanced hepatocellular carcinoma (HCC), but there remains a need for peripheral blood biomarkers to predict the clinical response. Here, we analyzed the peripheral blood of 45 patients with advanced HCC who underwent nivolumab. During treatment, frequency of classical monocytes (CD14⁺CD16^-) was increased on day 7, and the fold increase in the frequency on day 7 over day 0 (cMonocyte_D7/D0) was significantly higher in patients with durable clinical benefit (DCB) than in patients with non-DCB (NDB). When we analyzed transcriptomes of classical monocytes, CD274, gene encoding PD-L1, was upregulated in NDB patients compared to DCB patients at day 7. Notably, gene signature of suppressive tumor-associated macrophages, or IL4l1⁺PD-L1⁺IDO1⁺ macrophages, was enriched after treatment in NDB patients, but not in DCB patients. Accordingly, the fold increase in the frequency of PD-L1⁺ classical monocytes at day 7 over day 0 (cMonocyte-PDL1_D7/D0) was higher in NDB patients than DCB patients. The combined biomarker cMonocyte_D7/D0/cMonocyte-PDL1_D7/D0 was termed the "monocyte index", which was significantly higher in DCB patients than NDB patients. Moreover, the monocyte index was an independent prognostic factor for survival. Overall, our results suggest that early changes of circulating classical monocytes, represented as a monocyte index, could predict clinical outcomes of advanced HCC patients undergoing anti-PD-1 therapy.

SUBMITTER: Jeon SH

PROVIDER: S-EPMC9333050 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma.

Jeon Seung Hyuck SH Lee Yong Joon YJ Kim Hyung-Don HD Nam Heejin H Ryoo Baek-Yeol BY Park Su-Hyung SH Yoo Changhoon C Shin Eui-Cheol EC

Cancer immunology, immunotherapy : CII 20220728 2

Immune checkpoint inhibitors are effective for advanced hepatocellular carcinoma (HCC), but there remains a need for peripheral blood biomarkers to predict the clinical response. Here, we analyzed the peripheral blood of 45 patients with advanced HCC who underwent nivolumab. During treatment, frequency of classical monocytes (CD14+CD16-) was increased on day 7, and the fold increase in the frequency on day 7 over day 0 (cMonocyteD7/D0) was significantly higher in ...[more]

PMID: 35902399

Similar Datasets

Project description:BackgroundAlthough peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear.MethodsWe prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features.ResultsWe found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05).ConclusionCirculating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Project description:Purpose:To examine the effect of dynamic changes in neutrophil-to-lymphocyte ratio (NLR) on tumor response and overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Patients and Methods:Data from 181 patients with HCC were retrospectively collected. White blood cell, neutrophil and lymphocyte counts, and the NLR were obtained 1-3 days before as well as 3-6 weeks and 3 months after TACE. Patients were divided into two groups at each time point according to the mean value of NLR, and also divided into continuous decrease, fluctuating increase-decrease (I-D), fluctuating decrease-increase (D-I), and continuous increase groups according to the dynamic changes in the NLR. The dynamic changes in blood counts and NLR were analyzed using repeated-measures ANOVA. The odds ratios (ORs) for tumor response in different NLR groups were examined using a multivariate logistic regression model. Finally, the prognostic value of the dynamic changes in the NLR was examined using Cox regression models. Results:Continuous decline of white blood cell counts, neutrophil counts and lymphocyte counts were observed at 3-6 weeks and 3 months after TACE treatment. The NLR increased slightly and then decreased substantially in responders, while it increased slightly and then significantly in non-responders, with a significant interaction effect of Time × T?umor response (P = 0.005). NLR grouping before TACE, 3-6 weeks and 3 months after TACE was not associated with tumor response, and only 3 months after TACE did, it shows a significant difference in univariate survival analyse?s (NLR > 2.5 vs NLR ? 2.5, hazard ratio [HR] = 2.442, 95% confidence interval (CI): 1.545, 3.860). The changes in the NLR were significantly correlated with tumor response and OS. Non-responders for TACE were more common in the continuous NLR increase group (?OR = 6.230, 95% CI: 1.848-21.001) and in the fluctuating D-I group (OR = 5.702, 95% CI: 1.480-21.957). Multivariate analyses revealed that these two patient groups also showed poorer OS (HR = 2.351, 95% CI: 1.120-4.605 and HR = 2.320, 95% CI: 1.187-4.533, respectively). Conclusion:Dynamic changes in the NLR may be better predictors of tumor response and OS than static NLR values, but more data ?are needed.

Dataset Information

Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma.

Publications

Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets