Siglec-15 on macrophages suppress the immune microenvironment in patients with PD-L1 negative non-metastasis lung adenocarcinoma

Author:

Yang Lili1ORCID,Huang Ziqi,Guo Yan,Li Baihui,Shen Meng,Yi Yeran,Li Li,Zhao Xiaohe

Affiliation:

1. Tianjin Medical University Cancer Institute & Hospital

Abstract

Abstract Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immune checkpoint molecule with sequence homology to programmed cell death ligand 1 (PD-L1), which is mainly expressed on macrophages and tumor cells. However, whether Siglec-15 induced immunosuppression and poor prognosis are independent of PD-L1 remains unclear. In this study, we collected samples of 135 non-small cell lung cancer and found that Siglec-15 and PD-L1 expression were independent in non-small cell lung cancer by multiple immunofluorescence staining. Siglec-15 on macrophages (Mφ-Siglec-15) was significantly associated with DFS (p < 0.05) in PD-L1- patients with non-metastasis lung adenocarcinoma, not in PD-L1+ or lung squamous cell carcinoma patients. Moreover, stromal Siglec-15+ macrophages of Mφ-Siglec-15+PD-L1- patients were significantly more than those of Mφ-Siglec-15-PD-L1- patients (p = 0.002). We further found that Siglec-15+ macrophages were negatively associated with inflamed immunophenotype in PD-L1- patients and may inhibit CD8+T cells infiltration, validated in another independent cohort and in vivo. In conclusion, PD-L1-independent Siglec-15+ macrophages contribute to the formation of immunosuppressive microenvironment in non-metastasis lung adenocarcinoma patients, which may cause a higher risk of recurrence. Siglec-15 could be a potential target for normalizing cancer immunotherapy, benefiting patients who fail to respond to anti-PD-L1 therapy.

Publisher

Research Square Platform LLC

Reference30 articles.

1. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations;Zou W;Sci Transl Med,2016

2. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation;Wu M;J Hematol Oncol,2022

3. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung H;CA Cancer J Clin,2021

4. Lung cancer: some progress, but still a lot more to do;The L;Lancet (London, England),2019

5. PD-L1 in non-small-cell lung cancer: the third target for immunotherapy;Smit EF;Lancet (London, England),2016

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3