荷兰癌症研究所Daniela S. Thommen研究小组取得一项新突破。他们建立了剖析癌症中针对 PD-1 阻断反应的离体肿瘤片段平台。相关论文于2021年7月8日发表在《自然—医学》杂志上。

他们开发并采用了一种源自患者的肿瘤片段平台来剖析人类肿瘤组织对离体 PD-1 阻断的早期免疫反应。他们观察到免疫细胞在体外被重新激活的能力可以预测临床反应，扰动分析确定肿瘤驻留 T 细胞是这种免疫反应的关键组成部分。

此外，通过对基线特性和免疫反应能力的综合分析，他们确定了一个新的浸润性肿瘤亚组，该亚组缺乏对 PD-1 阻断反应的能力。最后，三级淋巴结构及其成分的基线存在与癌症进行肿瘤内免疫细胞再激活的能力相关。

据悉，PD-1 – PD-L1 轴抑制剂已被批准用于治疗多种人类癌症。尽管有证据表明它们具有广泛的临床活性，但对 PD-1 阻断后人类癌症组织中发生的免疫学改变知之甚少。

附：英文原文

Title: An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer

Author: Paula Voabil, Marjolein de Bruijn, Lisanne M. Roelofsen, Sanne H. Hendriks, Simone Brokamp, Marlous van den Braber, Annegien Broeks, Joyce Sanders, Petra Herzig, Alfred Zippelius, Christian U. Blank, Koen J. Hartemink, Kim Monkhorst, John B.A.G. Haanen, Ton N. Schumacher, Daniela S. Thommen

Issue&Volume: 2021-07-08

Abstract: Inhibitors of the PD-1–PD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation.

DOI: 10.1038/s41591-021-01398-3

Source: https://www.nature.com/articles/s41591-021-01398-3