肺腺癌中肿瘤和肿瘤相关巨噬细胞PD-L1表达欲辅助化疗的益处相关

SCI

23 October 2021

_{Tumor and Tumor-Associated Macrophage PD-L1 Expression is Associated with Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma}

_{(Journal of Thoracic Oncology, IF: 15.609)}

• Daniel J. Gross, Navin K. Chintala, Raj G. Vaghjiani, Rachel Grosser, Kay See Tan,Xiaoyu Li, Jennie Choe, Yan Li, Rania G. Aly, Katsura Emoto, Zheng Hua, JosephDux, Waseem Cheema, Matthew J. Bott, William D. Travis, James M. Isbell, Bob T.Li, David R. Jones, Prasad S. Adusumilli

• CORRESPONDENCE TO: [e-mail]

Introduction 导言

Patients with stage II-III lung adenocarcinoma are treated with adjuvant chemotherapy (ACT) to target the premetastatic niche that persists after curative-intent resection. We hypothesized that the premetastatic niche is a scion of resected lung tumor microenvironment (TME) and that analysis of TME can stratify survival benefit from ACT.

II-III期肺腺癌患者接受辅助化疗（ACT）以针对治疗性切除术后持续存在的转移前微环境。我们假设转移前微环境是切除的肺肿瘤微环境（TME）的后代，对TME的分析可以对ACT的生存效益进行分层。

Methods 方法

Using tumor and tumoral stroma from 475 treatment-naive patients with stage II-III lung adenocarcinoma, we constructed a tissue microarray and performed multiplex immunofluorescent staining for immune markers (programmed death ligand-1 [PD-L1], tumor-associated macrophages [TAMs], and myeloid-derived suppressor cells [MDSCs]), and derived myeloid-lymphoid ratio (MLR). The association between immune markers and survival was assessed using Cox models adjusted for pathologic stage.

利用475例未接受治疗的II-III期肺腺癌患者的肿瘤和肿瘤间质，我们构建了一个组织微阵列，并对免疫标记物（程序性死亡配体-1[PD-L1]、肿瘤相关巨噬细胞[TAMs]和髓源性抑制细胞[MDSCs]）进行多重免疫荧光染色，和衍生的髓样淋巴比（MLR）。免疫标记物与生存率之间的相关性采用经病理阶段调整的Cox模型进行评估。

Results 结果

Patients with high PD-L1 expression on TAMs or tumor cells in resected tumors had improved survival with ACT (TAMs: hazard ratio [HR], 1.79; 95% CI, 1.12-2.85; Tumor cells: HR, 3.02; 95% CI, 1.69-5.40). Among patients with high PD-L1 expression on TAMs alone or TAMs and tumor cells, ACT survival benefit is pronounced with high MLR (TAMs: HR, 3.87; 95% CI, 1.79-8.37; TAMs and tumor cells: HR, 2.19; 95% CI, 1.02-4.71) or with high stromal MDSC ratio (TAMs: HR, 2.53; 95% CI, 1.29-4.96; TAMs and tumor cells: HR, 3.21; 95% CI, 1.23-8.35). Patients with low/no PD-L1 expression on TAMs or tumor cells had no survival benefit from ACT.

TAMs或切除肿瘤的肿瘤细胞中PD-L1高表达的患者使用ACT可提高生存率（TAMs：危险比[HR]，1.79；95%CI，1.12-2.85；肿瘤细胞：HR，3.02；95%CI，1.69-5.40）。在仅有TAMs或TAMs与肿瘤细胞高PD-L1表达的患者中，高MLR（TAMs:HR，3.87；95%可信区间，1.79-8.37；TAMs与肿瘤细胞：HR，2.19；95%可信区间，1.02-4.71）或高基质MDSC比率（TAMs:HR，2.53；95%可信区间，1.29-4.96；TAMs与肿瘤细胞：HR，3.21；95%可信区间，1.23-8.35）的患者中，ACT生存率显著提高。TAMs或肿瘤细胞上PD-L1低/无表达的患者应用ACT后没有生存益处。

Conclusions 结论

Our observation that PD-L1 expression on TAMs or tumor cells is associated with improved survival with adjuvant chemotherapy provides rationale for prospective investigation and developing chemoimmunotherapy strategies for lung adenocarcinoma patients.

我们观察到在TAMs或肿瘤细胞上PD-L1表达与辅助化疗提高生存率相关，这为肺腺癌患者的前瞻性研究和开发化学免疫治疗策略提供了理论基础。

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