The C1q and gC1qR axis as a novel checkpoint inhibitor in cancer

被引:3
作者
Ghebrehiwet, Berhane [1 ,2 ]
Zaniewski, Michal [1 ]
Fernandez, Audrey [1 ]
Digiovanni, Mathew [1 ]
Reyes, Tiana N. [1 ]
Ji, Ping [1 ]
Savitt, Anne G. [1 ,3 ]
Williams, Jennie L. [1 ]
Seeliger, Markus A. [1 ,4 ]
Peerschke, Ellinor I. B. [5 ]
机构
[1] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Microbiol & Immunol, Stony Brook, NY USA
[4] SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY USA
[5] Mem Sloane Kettering Canc Ctr, Dept Lab Med, New York, NY USA
来源
FRONTIERS IN IMMUNOLOGY | 2024年 / 15卷
关键词
gC1qR; receptor for the globular "heads" of C1q; GHA; globular head A chain; C1QBP; the gene for gC1qR; CONTACT ACTIVATION SYSTEMS; SPLICING FACTOR SF2; BINDING-PROTEIN; GLOBULAR HEADS; MOLECULAR-CLONING; SURFACE PROTEIN; P-32; PROTEIN; EXPRESSION; RECEPTOR; CALRETICULIN;
D O I
10.3389/fimmu.2024.1351656
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Understanding at the molecular level of the cell biology of tumors has led to significant treatment advances in the past. Despite such advances however, development of therapy resistance and tumor recurrence are still unresolved major challenges. This therefore underscores the need to identify novel tumor targets and develop corresponding therapies to supplement existing biologic and cytotoxic approaches so that a deeper and more sustained treatment responses could be achieved. The complement system is emerging as a potential novel target for cancer therapy. Data accumulated to date show that complement proteins, and in particular C1q and its receptors cC1qR/CR and gC1qR/p33/HABP1, are overexpressed in most cancer cells and together are involved not only in shaping the inflammatory tumor microenvironment, but also in the regulation of angiogenesis, metastasis, and cell proliferation. In addition to the soluble form of C1q that is found in plasma, the C1q molecule is also found anchored on the cell membrane of monocytes, macrophages, dendritic cells, and cancer cells, via a 22aa long leader peptide found only in the A-chain. This orientation leaves its 6 globular heads exposed outwardly and thus available for high affinity binding to a wide range of molecular ligands that enhance tumor cell survival, migration, and proliferation. Similarly, the gC1qR molecule is not only overexpressed in most cancer types but is also released into the microenvironment where it has been shown to be associated with cancer cell proliferation and metastasis by activation of the complement and kinin systems. Co-culture of either T cells or cancer cells with purified C1q or anti-gC1qR has been shown to induce an anti-proliferative response. It is therefore postulated that in the tumor microenvironment, the interaction between C1q expressing cancer cells and gC1qR bearing cytotoxic T cells results in T cell suppression in a manner akin to the PD-L1 and PD-1 interaction.
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页数:9
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