Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma.
Nan Xiao,Xiao-Dong Zhu,Kangshuai Li,Yifan Chen,Xue-Feng Liu,Bin Xu,Ming Lei,Jiejie Xu,Hui-Chuan Sun +8 more
Reads0
Chats0
TLDR
Wang et al. as discussed by the authors showed that Siglec-10 was abundant in a large proportion of hepatocellular carcinoma (HCC) specimens and prominently distributed on macrophages.Abstract:
Tumor-associated macrophages (TAMs) promote key processes in the modulation of tumor microenvironment (TME). However, the clinical significance of heterogeneous subpopulations of TAMs in hepatocellular carcinoma (HCC) remains unknown. HCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas were obtained and analyzed. Immunohistochemistry and flow cytometry were performed to detect the characteristics of sialic acid-binding immunoglobulin-like lectin 10high (Siglec-10hi) TAMs and explore their impact on the TME of HCC. The effect of Siglec-10 blockade was evaluated in vitro based on fresh human tumor tissues. Our data revealed that Siglec-10 was abundant in a large proportion of HCC specimens and prominently distributed on macrophages. Kaplan–Meier curves and Cox regression analysis showed that intratumoral Siglec-10+ cell enrichment was associated with unfavorable prognosis in patients with HCC. Notably, multiple anti-inflammatory cytokines and inhibitory receptors were enriched in Siglec-10hi TAMs. RNA sequencing data also revealed that numerous M2-like signaling pathways were significantly upregulated in Siglec-10hi TAMs. High infiltration of Siglec-10hi TAMs was associated with impaired CD8+ T cell function in HCC. Of note, blocking Siglec-10 with the competitive binding antibody Siglec-10 Fc led to decreased expression of immunosuppressive molecules and increased the cytotoxic effects of CD8+ T cells against HCC cells. Moreover, blocking Siglec-10 promoted the anti-tumor efficacy of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab. Siglec-10hi TAMs are associated with immune suppression in the TME, and indicate poor prognosis in patients with HCC. Targeting Siglec-10hi TAMs may serve as a promising immunotherapy approach for HCC.read more
Citations
More filters
Journal ArticleDOI
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
TL;DR: In this article , the authors summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies, and focused on the advances of αPD- 1/PD L 1-based immunomodulatory strategies in clinical studies.
Journal ArticleDOI
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
TL;DR: In this paper , the authors summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies, and focused on the advances of αPD- 1/PD L 1-based immunomodulatory strategies in clinical studies.
Journal ArticleDOI
Targeting macrophages in hematological malignancies: recent advances and future directions
TL;DR: A review of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed is presented in this paper .
Journal ArticleDOI
Siglecs as Therapeutic Targets in Cancer.
TL;DR: Siglec-sialic acids are a family of nine-carbon α-keto acids found at the outermost ends of glycans attached to cell surfaces as mentioned in this paper.
Journal ArticleDOI
The intriguing roles of Siglec family members in the tumor microenvironment
TL;DR: In this article , the authors summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.
References
More filters
Journal ArticleDOI
Trimmomatic: a flexible trimmer for Illumina sequence data
TL;DR: Timmomatic is developed as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data and is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested.
Journal ArticleDOI
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.
TL;DR: EdgeR as mentioned in this paper is a Bioconductor software package for examining differential expression of replicated count data, which uses an overdispersed Poisson model to account for both biological and technical variability and empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference.
Journal ArticleDOI
HTSeq—a Python framework to work with high-throughput sequencing data
TL;DR: This work presents HTSeq, a Python library to facilitate the rapid development of custom scripts for high-throughput sequencing data analysis, and presents htseq-count, a tool developed with HTSequ that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes.
Journal ArticleDOI
Cancer statistics, 2020.
TL;DR: Slow momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers, and it is notable that long‐term rapid increases in liver cancer mortality have attenuated in women and stabilized in men.
Journal ArticleDOI
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation
Cole Trapnell,Cole Trapnell,Brian A. Williams,Geo Pertea,Ali Mortazavi,Gordon Kwan,Marijke J. van Baren,Steven L. Salzberg,Barbara J. Wold,Lior Pachter +9 more
TL;DR: The results suggest that Cufflinks can illuminate the substantial regulatory flexibility and complexity in even this well-studied model of muscle development and that it can improve transcriptome-based genome annotation.