1.PD-1 antibody enhanced anti-tumor efficacy of oxaliplatin against colon cancer in vitro and in vivo
ZHONG Genshen1a ; SUN Zhiyang1a ; CHEN Yanan1a ; XU Zhishan1c ; YANG Ru1c ; WU Minna1d ; SHI Huan2 ; LU Ping1a
Chinese Journal of Cancer Biotherapy 2018;25(10):999-1005
Objective: To explore the anti-tumor effects of oxaliplatin (OXA) combined with PD-1 antibody on colon cancer. Methods: Flow cytometry was used to detect the expression of PD-L1 in colon cancer cell lines HCT-116 and HT-29. Co-culture method was used to detect the secretion of cytokines and the changes of CD4/CD8 subsets in T-cells that co-cultured with HCT-116 cells, which were pretreated with OXAin combination with/without PD-1 antibody; The CT26 transplanted tumor model of colon cancer in BALB/c mice was established and treated with the combination of OXA and PD-1 to evaluate their anti-tumor efficacy. Meanwhile, CD8 antibody was used to scavenge CD8+ T cells in mice, and to evaluate the role of CD8+ T cells in the anti-tumor effect of OXA in vivo. Results: OXAcould significantly increase the expression of PD-L1 on the surface of colon cancer cells. Compared with pure T-cells, the T cells co-cultured with colon cancer HCT-116 cells that pre-treated by OXA, exhibited significantly reduced IL-2, IFN-γ and TNF levels (all P<0.05) in its culture supernatant and decreased ratio of CD4+memory T cell / CD8+TEMER (P<0.05), whereas there was increased cell proportion of the CD4+ (P>0.05) and CD8+ (P<0.05) naïve T cells. After co-treated with PD-1 antibody, compared with the single treatment of OXA, IFN-γ and IL-10 content (P<0.05) in culture supernatant and the subsets of CD8+ TCM and TEMRA ratio (P>0.05) were increased. In vivo experiments showed that OXAcombined with PD-1 antibody could enhance its anti-tumor activity, the tumor suppression rates were 25.6% (OXA) and 29.1% (αPD-1), respectively, however, the rate of tumor inhibition was increased to 58.2% when combined (P<0.05, compared to OXA or αPD-1 group). After scavenging CD8+T cells in mice, the antitumor activity of OXA dropped from 68.4% to 46.2% (P<0.05). Conclusion: OXA combined with PD-1 antibody had synergistic anti-tumor effect, and CD8+ T cells played an important role in the antitumor activity of OXA.
2.Predictive value of prognostic nutritional index for treatment efficacy and prognosis in locally advanced esophageal squamous cell carcinoma patients treated with chemotherapy combined with immune sequential radiotherapy
WANG Yu1,2 ; WEI Zhuojun2 ; WANG Lin3 ; WANG Ruiqi4 ; CHEN Huan2 ; CHENG Qi2 ; LIN Xiao2 ; MA Honglian2 ; XU Yujin2
Chinese Journal of Cancer Biotherapy 2025;32(4):405-412
[摘 要] 目的:探索预后营养指数(PNI)在接受诱导化疗联合免疫(化免)序贯放疗的局部晚期食管鳞状细胞癌(ESCC)中的疗效预测价值及预后影响。方法: 回顾性分析浙江省肿瘤医院2019年5月至2023年8月期间收治的126例行诱导化免序贯放疗的局部晚期ESCC患者的临床资料。绘制受试者工作特征曲线(ROC曲线),确定患者诱导化免前1周内、放疗前1周内、放疗开始后4 ± 1周的PNI最佳临界值并对患者进行分组。采用Kaplan-Meier法绘制生存曲线,并用Log-Rank法比较组间患者的总生存期(OS)及无进展生存期(PFS),采用Cox回归分析探讨诱导化免序贯放疗的局部晚期ESCC患者的预后影响因素。结果: 共纳入126例局部晚期ESCC患者,男性118例,女性8例,中位年龄65岁(44~78岁)。运用ROC曲线确认的患者诱导化免前、放疗前和放疗中PNI最佳临界值为46.2、48.3和37.9。放疗前PNI ≥ 48.3组中位OS、PFS分别为47.3、28.2个月,放疗前PNI < 48.3组中位OS、PFS分别为18.7、15.2个月(P < 0.01,P < 0.05)。放疗中PNI ≥ 37.9组中位OS未达到,中位PFS为25.7个月,放疗中PNI < 37.9组中位OS、PFS分别为17.0、12.5个月(P < 0.01,P < 0.05)。诱导化免后PNI升高组中位OS未达到,中位PFS为28.4个月;PNI降低组中位OS、PFS分别为20.4、16.0个月(P < 0.01,P < 0.05)。多因素分析显示,放疗中PNI[HR = 2.292,95% CI(1.264,4.159),P < 0.05]、诱导化免后PNI变化[HR = 2.120, 95% CI(1.007, 4.463),P < 0.05]为影响OS因素。结论: 放疗中PNI、诱导化免后PNI变化与患者治疗疗效及预后有一定相关性,可作为预测ESCC化免序贯放疗获益的重要指标。