Abstract

Background

Patients selected based on PD-L1 expression for second-line immune checkpoint inhibitor (ICI) treatment are often identified using archival specimens collected months or years prior to starting immunotherapy. Such patients may have received and failed multiple lines of standard of care (SOC) treatments with subsequent potential impact on PD-L1 expression and immune microenvironment.

Methods

We have analysed formalin fixed paraffin embedded (FFPE) tissues in a cohort of NSCLC patients (n = 16) taken during resection performed as first-line surgical treatment for which radiotherapy, SOC chemotherapy, and second-line immunotherapy clinical follow-up data are available. The immune microenvironment was evaluated by immunohistochemistry (IHC) plus digital image analysis for CD3, CD8, PD-L1, CD68 and CD163, and by Nanostring using the IO360^TM gene expression panel, with the aim of exploring whether immune signatures predictive of response to ICI therapy may be identified in such samples.

Results

Clinical follow-up data indicated objective response to ICI therapy for 4/16 patients (n = 2 Nivolumab, n = 1 Pembrolizumab, n = 1 Durvalumab) with time from first diagnosis to receiving second-line ICI treatment ranging from 5 to 102 (mean 33.6) months. During this time these patients received various lines of radiotherapy and SOC chemotherapy prior to receiving immunotherapy. While the Tumor Inflammation Signature was not predictive of response, gene expression analysis did identify several signatures associated significantly with response, including increased abundance of CD8 T cells, cytotoxic cells, cytotoxicity, MHC class II antigen presentation and Melanoma-Associated Antigens (MAGE). These data were supported by a significant elevation of CD8 T cells by IHC in the responder versus non-responder populations, from a mean of 329 to 961 CD8+ T cells/mm².

Conclusion

Taken together these data demonstrate that despite various lines of previous radiotherapy and chemotherapy spanning several years, immune profiles associated with response to second-line immunotherapy can be detected in surgical first-line resection samples.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Bhagat: Shareholder / Stockholder / Stock options, Officer / Board of Directors: TriStar Technolgoy Group. All other authors have declared no conflicts of interest.

中文翻译：

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135P治疗前非小细胞肺癌（NSCLC）患者的免疫微环境分析及对二线免疫治疗的随访反应数据

抽象的

背景

基于PD-L1表达选择用于二线免疫检查点抑制剂（ICI）治疗的患者通常使用开始免疫治疗前数月或数年收集的档案标本进行鉴定。此类患者可能已经接受了多行标准护理（SOC）治疗并因此而失败，从而对PD-L1表达和免疫微环境产生了潜在的影响。

方法

我们分析了一组在切除期间作为一线外科手术治疗的NSCLC患者（n = 16）中的福尔马林固定石蜡包埋（FFPE）组织，作为一线外科治疗，其放射治疗，SOC化疗和二线免疫治疗的临床随访数据为可用的。免疫微环境通过免疫组织化学（IHC）加上CD3，CD8，PD-L1，CD68和CD163的数字图像分析进行评估，并使用IO360 ^TM基因表达面板通过Nanostring进行评估，目的是探讨免疫信号是否可预测对在这些样品中可以鉴定出ICI疗法。

结果

临床随访数据表明，从初次诊断到接受二线ICI治疗的时间从4到16位患者（n = 2尼武单抗，n = 1帕姆单抗，n = 1 Durvalumab）对ICI治疗的客观反应范围为5至102（平均33.6）个月。在这段时间内，这些患者在接受免疫治疗之前接受了各种放疗和SOC化疗。尽管肿瘤炎症特征不能预测反应，但基因表达分析确实发现了与反应显着相关的几个特征，包括CD8 T细胞，细胞毒性细胞，细胞毒性，MHC II类抗原呈递和黑色素瘤相关抗原（MAGE）的丰度增加。这些数据得到了IHC在应答者和非应答者群体中CD8 T细胞显着升高的支持，²。

结论

这些数据加在一起表明，尽管过去的放疗和化学疗法历经数年，但在外科手术一线切除样品中仍可检测到与对二线免疫疗法反应相关的免疫谱。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

M. Bhagat：股东/股东/股票期权，官员/董事会：TriStar Technolgoy Group。所有其他作者都声明没有利益冲突。