Mazzaschi G, Minari R, Zecca A, Cavazzoni A, Ferri V, Mori C, Squadrilli A, Bordi P, Buti S, Bersanelli M, Leonetti A, Cosenza A, Ferri L, Rapacchi E, Missale G, Petronini P G, Quaini F, Tiseo M
Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine & Surgery, University of Parma, Italy.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Lung Cancer. 2020 Oct;148:1-11. doi: 10.1016/j.lungcan.2020.07.028. Epub 2020 Aug 2.
Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC).
Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD-1+ and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (IS). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response.
High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P < 0.001), OS (P < 0.01) and ICI-response (P < 0.05). Thus, sPD-L1, CD8+PD-1+ and NK were considered as risk factors encompassing IS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IS characterizing patients with significantly (P < 0.001) prolonged PFS (median NR vs 2.3 months) and OS (median NR vs 4.1) and greater benefit from ICIs (P < 0.01). We then combined each risk parameter composing IS and LIPI (LDH, dNLR), thus defining three distinct prognostic classes. A remarkable impact of IS-LIPI integration was documented on survival outcome (PFS, HR = 4.61; 95%CI = 2.32-9.18; P < 0.001; OS, HR=4.03; 95%CI=1.91-8.67; P < 0.001) and ICI-response (AUC=0.90, 95%CI=0.81-0.97, P < 0.001).
Composite risk models based on blood parameters featuring the tumor-host interaction might provide accurate prognostic scores able to predict ICI benefit in NSCLC patients.
目前尚远未确定可预测免疫检查点抑制剂（ICI）疗效的前期标准。因此，我们整合了促炎/免疫抑制或有效的抗肿瘤反应的血液指标，以非侵入性方式定义接受ICI治疗的晚期非小细胞肺癌（NSCLC）患者的预测性免疫图谱。
前瞻性收集了109例连续接受ICI作为一线或多线治疗的NSCLC患者基线时的外周血（PB）。评估可溶性PD-L1（sPD-L1）（免疫测定法）、CD8+PD-1+和NK（流式细胞术）细胞，并将其交织以生成免疫效应评分（IS）。通过乳酸脱氢酶（LDH）水平和衍生的中性粒细胞与淋巴细胞比值（dNLR）计算肺免疫预后指数（LIPI）。所有这些参数均与生存结果和治疗反应相关。
高sPD-L1、低CD8+PD-1+和NK数量对无进展生存期（PFS）（P<0.001）、总生存期（OS）（P<0.01）和ICI反应（P<0.05）有负面影响。因此，sPD-L1、CD8+PD-1+和NK被视为包含IS的危险因素，其预后能力优于个体特征，略超过LIPI。相应地，不存在这些危险因素描绘了一种有利的IS，其特征是患者的PFS（中位数未达到对比2.3个月）和OS（中位数未达到对比4.1个月）显著延长（P<0.001），并且从ICI中获益更大（P<0.01）。然后，我们将构成IS和LIPI的每个风险参数（LDH、dNLR）组合起来，从而定义了三个不同的预后类别。IS-LIPI整合对生存结果（PFS，风险比[HR]=4.61；95%置信区间[CI]=2.32-9.18；P<0.001；OS，HR=4.03；95%CI=1.91-8.67；P<0.001）和ICI反应（曲线下面积[AUC]=0.90，95%CI=0.81-0.97，P<0.001）有显著影响。
基于以肿瘤-宿主相互作用为特征的血液参数的复合风险模型可能提供准确的预后评分，能够预测NSCLC患者从ICI中获益的情况。
