Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Laboratory of Clinical and Experimental Pathology, Biobank Côte d'Azur BB-0033-00025, FHU OncoAge, IHU RespirERA, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
Br J Cancer. 2023 Oct;129(9):1417-1431. doi: 10.1038/s41416-023-02318-7. Epub 2023 Jun 30.
The past decade has witnessed a revolution in cancer treatment by the shift from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular the immune-checkpoint inhibitors (ICIs). These immunotherapies selectively release the host immune system against the tumour and have shown unprecedented durable remission for patients with cancers that were thought incurable such as advanced non-small cell lung cancer (aNSCLC). The prediction of therapy response is based since the first anti-PD-1/PD-L1 molecules FDA and EMA approvals on the level of PD-L1 tumour cells expression evaluated by immunohistochemistry, and recently more or less on tumour mutation burden in the USA. However, not all aNSCLC patients benefit from immunotherapy equally, since only around 30% of them received ICIs and among them 30% have an initial response to these treatments. Conversely, a few aNSCLC patients could have an efficacy ICIs response despite low PD-L1 tumour cells expression. In this context, there is an urgent need to look for additional robust predictive markers for ICIs efficacy in thoracic oncology. Understanding of the mechanisms that enable cancer cells to adapt to and eventually overcome therapy and identifying such mechanisms can help circumvent resistance and improve treatment. However, more than a unique universal marker, the evaluation of several molecules in the tumour at the same time, particularly by using multiplex immunostaining is a promising open room to optimise the selection of patients who benefit from ICIs. Therefore, urgent further efforts are needed to optimise to individualise immunotherapy based on both patient-specific and tumour-specific characteristics. This review aims to rethink the role of multiplex immunostaining in immuno-thoracic oncology, with the current advantages and limitations in the near-daily practice use.
过去十年见证了癌症治疗的革命，从传统药物（化疗）转向靶向分子疗法和免疫疗法，特别是免疫检查点抑制剂（ICI）。这些免疫疗法选择性地释放宿主免疫系统对肿瘤的攻击，为那些被认为无法治愈的癌症患者（如晚期非小细胞肺癌[aNSCLC]）带来了前所未有的持久缓解。自第一个抗 PD-1/PD-L1 分子 FDA 和 EMA 批准以来，治疗反应的预测一直基于免疫组化评估的肿瘤细胞 PD-L1 表达水平，最近在美国也或多或少基于肿瘤突变负担。然而，并非所有 aNSCLC 患者都能平等地从免疫治疗中获益，因为只有约 30%的患者接受了 ICI，其中 30%的患者对这些治疗有初始反应。相反，尽管 aNSCLC 患者的肿瘤细胞 PD-L1 表达水平较低，仍有少数患者可能对 ICI 有疗效反应。在这种情况下，迫切需要寻找其他强大的预测标志物来评估 ICI 在胸科肿瘤学中的疗效。了解使癌细胞能够适应并最终克服治疗的机制，并识别这些机制，有助于规避耐药性并改善治疗效果。然而，评估肿瘤中多个分子的多重免疫染色，而不仅仅是单一的普遍标志物，是优化选择受益于 ICI 的患者的一个有前途的方向。因此，迫切需要进一步努力，根据患者和肿瘤的特定特征，优化个体化免疫治疗。本文旨在重新思考多重免疫染色在免疫胸科肿瘤学中的作用，以及当前在日常实践中的优势和局限性。
