Department of Interventional Therapy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangdong Provincial Key laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Immunol. 2024 Feb 9;15:1325330. doi: 10.3389/fimmu.2024.1325330. eCollection 2024.
Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear.
We 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.
We 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).
Circulating 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.
外周血淋巴细胞亚群，尤其是 PD-1+T 细胞，是癌症患者有前景的预后指标。然而，其临床意义尚不清楚。
我们前瞻性纳入了 157 例接受经导管动脉化疗栓塞联合或不联合 PD-1 抑制剂治疗的肝细胞癌（HCC）患者。分析了 20 种外周血淋巴细胞亚群和细胞因子。分析了 PD-1 抑制剂治疗与未治疗患者 PD-1+T 细胞的差异及其与肿瘤反应、生存预后和临床特征的关系。
我们发现，接受 PD-1 抑制剂治疗的患者基线 CD8+PD-1+和 CD4+PD-1+T 细胞频率低于未接受 PD-1 抑制剂治疗的患者（p<0.001）。在前者患者中，应答亚组和无应答亚组 PD-1+T 细胞频率无差异（p>0.05），而在后者患者中，CD8+PD-1+T 细胞、CD4+PD-1+T 细胞和 CD8+PD-1+/CD4+PD-1+比值水平不能预测肿瘤反应、无进展生存期（PFS）或总生存期（OS）（p>0.05）。此外，多因素分析显示，CD8+CD38+T 细胞水平（OR=2.806，p=0.006）与肿瘤反应相关，而 CD8+CD28+T 细胞（p=0.038，p=0.001）和自然杀伤（NK）细胞（p=0.001，p=0.027）与 PFS 和 OS 相关。尽管这些独立的预后因素与肿瘤进展特征相关（p<0.05），但除 CD8+CD28+T 细胞外，治疗前后这些因素的变化与肿瘤反应无关（p>0.05）。
循环 CD8+CD38+T 细胞、CD8+CD28+T 细胞和 NK 细胞被确定为 HCC 患者肿瘤反应和生存的潜在预后因素。相反，尽管 PD-1 抑制剂能有效阻断 T 细胞 PD-1 受体，但基线 PD-1+T 细胞频率及其频率变化的预后价值有限。
