PD-1/PD-L1檢查點抑制腫瘤引流淋巴結中的T細胞免疫
作者：
小柯機器人發布時間：2020/10/4 23:01:47
荷蘭伊拉斯姆斯大學Joachim G. Aerts等研究人員合作發現，PD-1/PD-L1檢查點抑制腫瘤引流淋巴結中的T細胞免疫。這一研究成果於2020年10月1日在線發表在國際學術期刊《癌細胞》上。
研究人員在小鼠腫瘤模型中發現，引流淋巴結（TDLN）富含與PD-L1+常規樹突狀細胞（cDC）緊密相關的腫瘤特異性PD-1+T細胞。TDLN靶向的PD-L1阻斷通過在腫瘤部位播種祖細胞耗盡的T細胞，從而增強了抗腫瘤T細胞免疫力，進而改善了腫瘤控制。
此外，研究人員表明非轉移性黑色素瘤患者的TDLN中有大量PD-1/PD-L1相互作用，而相應腫瘤中的PD-1/PD-L1相互作用卻與較早的疾病復發相關。這些發現指出了TDLN中PD-L1表達在控制全身抗腫瘤免疫中的關鍵作用，從而鑑定了可通過輔助PD-1/PD-L1阻斷療法改善的高危患者群體。
據了解，通常認為PD-1/PD-L1-檢查點阻斷療法可減輕腫瘤微環境中腫瘤細胞介導的抑制作用，但PD-L1也可在非腫瘤巨噬細胞和cDC中表達。
附：英文原文
Title: The PD-1/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes
Author: Floris Dammeijer, Mandy van Gulijk, Evalyn E. Mulder, Melanie Lukkes, Larissa Klaase, Thierry van den Bosch, Menno van Nimwegen, Sai Ping Lau, Kitty Latupeirissa, Sjoerd Schetters, Yvette van Kooyk, Louis Boon, Antien Moyaart, Yvonne M. Mueller, Peter D. Katsikis, Alexander M. Eggermont, Heleen Vroman, Ralph Stadhouders, Rudi Hendriks, Jan von der Thüsen, Dirk J. Grünhagen, Cornelis Verhoef, Thorbald van Hall, Joachim G. Aerts
Issue&Volume: 2020-10-1
Abstract: PD-1/PD-L1-checkpoint blockade therapy is generally thought to relieve tumor cell-mediatedsuppression in the tumor microenvironment but PD-L1 is also expressed on non-tumormacrophages and conventional dendritic cells (cDCs). Here we show in mouse tumor modelsthat tumor-draining lymph nodes (TDLNs) are enriched for tumor-specific PD-1+ T cells which closely associate with PD-L1+ cDCs. TDLN-targeted PD-L1-blockade induces enhanced anti-tumor T cell immunity byseeding the tumor site with progenitor-exhausted T cells, resulting in improved tumorcontrol. Moreover, we show that abundant PD-1/PD-L1-interactions in TDLNs of nonmetastaticmelanoma patients, but not those in corresponding tumors, associate with early distantdisease recurrence. These findings point at a critical role for PD-L1 expression inTDLNs in governing systemic anti-tumor immunity, identifying high-risk patient groupsamendable to adjuvant PD-1/PD-L1-blockade therapy.
DOI: 10.1016/j.ccell.2020.09.001
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30432-3