小柯机器人

美国基因泰克公司Sanjeev Mariathasan、Mahrukh A. Huseni等研究人员合作发现，肿瘤相关的IL-8与PD-L1阻断剂的临床疗效降低有关。该项研究成果发表在2020年5月11日的《自然—医学》上。

Title: High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade

Author: Kobe C. Yuen, Li-Fen Liu, Vinita Gupta, Shravan Madireddi, Shilpa Keerthivasan, Congfen Li, Deepali Rishipathak, Patrick Williams, Edward E. Kadel, Hartmut Koeppen, Ying-Jiun Chen, Zora Modrusan, Jane L. Grogan, Romain Banchereau, Ning Leng, AnnChristine Thastrom, Xiadong Shen, Kenji Hashimoto, Darren Tayama, Michiel S. van der Heijden, Jonathan E. Rosenberg, David F. McDermott, Thomas Powles, Priti S. Hegde, Mahrukh A. Huseni, Sanjeev Mariathasan

Issue&Volume: 2020-05-11

Abstract: Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade1, this has not been comprehensively evaluated in large randomized studies. Here we analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8+T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors.

DOI: 10.1038/s41591-020-0860-1

Source: https://www.nature.com/articles/s41591-020-0860-1

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex