Araujo B de Lima Vinicius, Hansen Morten, Spanggaard Iben, Rohrberg Kristoffer, Reker Hadrup Sine, Lassen Ulrik, Svane Inge Marie
Department of Oncology, Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark.
National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.
Front Oncol. 2021 Mar 25;11:558248. doi: 10.3389/fonc.2021.558248. eCollection 2021.
Despite encouraging results with immune checkpoint inhibition (ICI), a large fraction of cancer patients still does not achieve clinical benefit. Finding predictive markers in the complexity of the tumor microenvironment is a challenging task and often requires invasive procedures. In our study, we looked for putative variables related to treatment benefit among immune cells in peripheral blood across different tumor types treated with ICIs. For that, we included 33 patients with different solid tumors referred to our clinical unit for ICI. Peripheral blood mononuclear cells were isolated at baseline, 6 and 20 weeks after treatment start. Characterization of immune cells was carried out by multi-color flow cytometry. Response to treatment was assessed radiologically by RECIST 1.1. Clinical outcome correlated with a shift towards an effector-like T cell phenotype, PD-1 expression by CD8+T cells, low levels of myeloid-derived suppressor cells and classical monocytes. Dendritic cells seemed also to play a role in terms of survival. From these findings, we hypothesized that patients responding to ICI had already at baseline an immune profile, here called 'favorable immune periphery', providing a higher chance of benefitting from ICI. We elaborated an index comprising cell types mentioned above. This signature correlated positively with the likelihood of benefiting from the treatment and ultimately with longer survival. Our study illustrates that patients responding to ICI seem to have a pre-existing immune profile in peripheral blood that favors good outcome. Exploring this signature can help to identify patients likely to achieve benefit from ICI.
尽管免疫检查点抑制(ICI)取得了令人鼓舞的结果,但仍有很大一部分癌症患者未获得临床益处。在肿瘤微环境的复杂性中寻找预测标志物是一项具有挑战性的任务,通常需要侵入性操作。在我们的研究中,我们在接受ICI治疗的不同肿瘤类型患者的外周血免疫细胞中寻找与治疗益处相关的假定变量。为此,我们纳入了33例因ICI转诊至我们临床科室的不同实体瘤患者。在治疗开始时、治疗后6周和20周采集外周血单个核细胞。通过多色流式细胞术对免疫细胞进行表征。根据RECIST 1.1通过影像学评估治疗反应。临床结果与向效应样T细胞表型的转变、CD8 + T细胞的PD-1表达、髓系来源抑制细胞和经典单核细胞的低水平相关。树突状细胞似乎在生存方面也发挥了作用。基于这些发现,我们假设对ICI有反应的患者在基线时就已经具有一种免疫特征,这里称为“有利的免疫外周”,从而有更高的机会从ICI中获益。我们制定了一个包含上述细胞类型的指数。该特征与从治疗中获益的可能性呈正相关,并最终与更长的生存期相关。我们的研究表明,对ICI有反应的患者在外周血中似乎有一种预先存在的免疫特征,有利于良好的预后。探索这种特征有助于识别可能从ICI中获益的患者。