C3d regulates immune checkpoint blockade and enhances antitumor immunity

Platt, Jeffrey L.; Silva, Inês; Balin, Samuel J.; Lefferts, Adam R.; Farkash, Evan A.; Ross, Ted M.; Carroll, Michael; Cascalho, Marília

doi:10.1172/jci.insight.90201

Cited by 25 publications

(29 citation statements)

References 37 publications

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“…Complement can kill tumor cells through complement-dependent cytotoxicity, which is an important mechanism for tumor killing by monoclonal Ab. C3d enhanced antitumor immunity by increasing tumor-infiltrating CD8 + T cells, depleting Tregs, and suppressing PD-1 expression on T cells (45). In addition, complement activation in tumor vasculature facilitated T cell homing and control of tumor in adoptive cellular therapy (46).…”

Section: Discussionmentioning

confidence: 99%

Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment

Singel¹,

Emmons²,

Khan³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment

Singel¹,

Emmons²,

Khan³

et al. 2019

JCI Insight

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“…Cys We have also found that C3d encoded in the vaccine can amplify protective cell-mediated immune responses to tumor antigens in target cells independent of responses to antigens encoded in the construct [42]. We do not assume the vaccine will anticipate all or even most antigenic variants that would be generated after infection occurs.…”

Section: Discussionmentioning

confidence: 90%

“…Rather, the vaccine would hopefully anticipate enough variants either to eradicate the virus before extensive replication occurs or to slow viral evolution enough to allow immunity to recognize and control those variants that 'escape' representation by the vaccine. It is also possible that enhanced cellular immunity conferred by C3d [42] could slow viral replication and hence evolution independent of the particular variants produced. Given the diversity of HIV in the community and the reliance of the vaccine (much like the virus) on random errors, we think it unlikely that even a fully optimized mutable vaccine could anticipate and prevent infection by all viral variants in the community.…”

Section: Discussionmentioning

confidence: 99%

“…The mutable vaccine for mutable viruses Perspective e xpression [40]; three copies of complement (in frame with env) to decrease the threshold for immunogenicity in T cell-dependent B-cell responses [41] and to enhance cell-mediated immunity independent of B cells [42]; and the Ig heavy chain large intronic enhancer (Eμ) to confer hypermutability. The gene product is assembled and secreted as a trimer, enhancing immunogenicity still further [40].…”

Section: Eµ-λ1pmentioning

confidence: 99%

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The Mutable Vaccine for Mutable Viruses

2017

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Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies. The vaccine consists of a DNA construct encoding viral antigen and regulatory sequences that upon delivery to B cells target the enzymatic apparatus of 'somatic hypermutation' causing the construct to mutate one million-times baseline rates and allowing production and presentation of antigen variants. We postulate the mutable vaccine might thus anticipate diversification of mutable viruses, allowing direct control or slowing of evolution. Initial work presented here should encourage consideration of this novel approach.

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“…Complement receptor 3 (CR3; Mac-1; CD11b/CD18) mediates neutrophils recruitment and adhesion by binding to ICAM-1 on endothelial and T cells. C3d plays a central role in the complement system, and enhances antitumor immunity by increasing tumor-infiltrating CD8+ T cells, depleting Tregs, and suppressing PD-1 expression on T cells (140). Ascites from patients with high-grade serous ovarian cancer (HGSOC) can induce the suppressor phenotype in neutrophils from healthy donors (141).…”

Section: Neutrophils and Immunosuppressionmentioning

confidence: 99%

Neutrophil: A New Player in Metastatic Cancers

Tan

et al. 2020

Front. Immunol.

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The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an "audience" in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, with a specific focus on their pro-metastatic functions. We also discuss the potential and challenges of neutrophils as therapeutic targets. A better understanding the role of neutrophils in cancer will discover new mechanisms of metastasis and develop new immunotherapies by targeting neutrophils.

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C3d regulates immune checkpoint blockade and enhances antitumor immunity

Cited by 25 publications

References 37 publications

Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment

Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment

The Mutable Vaccine for Mutable Viruses

Neutrophil: A New Player in Metastatic Cancers

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