Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1
By D. Kuang, Qiyi Zhao, C. Peng, Jing Xu, Jing-Ping Zhang, Changyou Wu, Limin Zheng. Journal of Experimental Medicine, 2009
845 citations recorded by the source corpus.
Macrophages (Mφ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mφ to trigger transient activation of monocytes in peritumoral stroma. We showed that a fraction of monocytes/Mφ in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC). Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1+ and HLA-DRhigh on tumor-infiltrating monocytes. Autocrine tumor necrosis factor α and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1+ monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes. Moreover, we found that PD-L1 expression on tumor-infiltrating monocytes increased with disease progression, and the intensity of the protein was associated with high mortality and reduced survival in the HCC patients. Thus, expression of PD-L1 on activated monocytes/Mφ may represent a novel mechanism that links the proinflammatory response to immune tolerance in the tumor milieu.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/c34e3cb9f981d1d7b52a9e40d03c3845df1ceb39
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Citations in the corpus
- The blockade of immune checkpoints in cancer immunotherapy (2012, background): “In addition to tumour cells, PDL1 is commonly expressed on myeloid cells in the tumour microenvironmen”
- Tumor-associated macrophages: from mechanisms to therapy (2014, background): “Similarly, monocytes from patients with hepatocellular carcinoma express PD-L1 that contributes to human tumor xenograft growth in vivo, while the blocking of PD-L1 reverses this effect (Kuang et al., 2009).”
- Macrophages and therapeutic resistance in cancer (2015, positive): “That said, CD14 myeloid cells from hepatocellular and ovarian carcinomas suppress autologous T cell proliferation and IFN-g expression in vitro and nullify anti-tumor T cell activity during in vivo adoptive transfer experiments (Kryczek et al., 2006; Kuang et al., 2009).”
- Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells (2014, background): “Human macrophages have instead been found to directly suppress T cell responses through programmed death-ligand 1 in hepatocellular carcinoma (Kuang et al., 2009) and B7-H4 in ovarian carcinoma (Kryczek et al., 2006), and possibly indirectly through TReg cell recruitment through CCL22 (Curiel et…”
- Coordinated regulation of myeloid cells by tumours (2012, background): “TAMs can also cause T cell apoptosis through their expression of PD1 ligand 1 (PDL1), which binds to its receptor programmed cell death protein 1 (PD1) on activated T cell”
- Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment (2014, background): “PD-L1-positive monocytes induced T cell dysfunction, as defined by the presence of low cytotoxicity to tumor cells and a reduction in T cell proliferation [90].”
- Advances in immunotherapy for hepatocellular carcinoma (2021, background): “I.M. receives funding from MINECO SAF2014-52361-R and SAF 2017- 83267-C2-1R; Worldwide Cancer Research Grant (15-1146); the Asociacion Española Contra el Cancer (AECC) Foundation under grant GCB15152947MELE; and the European Union’s Horizon 2020 Program (grant agreement no. 635122 PROCROP).”
- Accessories to the crime: functions of cells recruited to the tumor microenvironment. (2012, positive): “…L-arginine metabolism (Kryczek et al., 2006) and may instead rely on macrophage expression of ligands for T cell costimulatory receptors that mediate T cell inhibition (Topalian et al., 2012), as has been described for hepatocellular (Kuang et al., 2009) and ovarian (Kryczek et al., 2006) cancer.”