Localized immune transcriptional response to intratumorally administrated TLR7 agonist conjugates

Abstract

Induced or circumstantial immunosuppression present opportunities for cancer development, and progression. Recently, multiple therapies have been developed to harness the immune system's ability to selectively eradicate cancer cells. These approaches have primarily targeted features of the adaptive immune response such as checkpoint blockade and vaccination of tumorigenic peptides. Toll‐Like receptors (TLRs) are innate immune receptors that recognize molecules broadly shared by various pathogens. TLR pathways are increasingly targeted in cancer immunotherapy approaches seeking to overcome immune‐evasion by cancer cells. Here, we hypothesize that activation of TLR7, an endosomal receptor which recognizes pathogen associated nucleic acids, can mitigate tumor immunosuppression. TLR7 agonist (TLR7‐A) conjugated to silica nanoparticles will be used as an adjuvant in a mouse colon adenocarcinoma (CT26 cell line derived) in vivo tumor model. Transcriptional targets of adaptive immune cells (CD3, CD4, CD8, Granzyme B and Perforin), antigen presenting cells (MHCII, CD80, CD86 and CD40) and inflammatory cytokine response (TNFα, IL‐6, IP‐10, MCP1, MIP1α and IFNγ) were measured by qPCR in tumor tissue following 21 days of treatment. We found that treatment with TLR7‐A unconjugated and conjugated increased localized transcript levels of inflammatory cytokines and chemokines: IL‐6, IP‐10, MCP1, MIP1α and IFNγ. This project will provide valuable insights on the distinct transcriptional immune interplay in response to TLR7‐A treatment (localized vs systemic), support the decision‐making process of subsequent experimental approaches and evaluate TLR7‐A conjugate's potential for treatment.Support or Funding InformationThis research was supported by the National Cancer Institute of the National Institutes of Health under award numbers:U54CA132384 & U54CA132379This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.