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Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity.

Publication ,  Journal Article
Brown, M
Published in: Cancer Treat Res
2022

Malignant tumors frequently exploit innate immunity to evade immune surveillance. The priming, function, and polarization of antitumor immunity fundamentally depends upon context provided by the innate immune system, particularly antigen presenting cells. Such context is determined in large part by sensing of pathogen specific and damage associated features by pathogen recognition receptors (PRRs). PRR activation induces the delivery of T cell priming cues (e.g. chemokines, co-stimulatory ligands, and cytokines) from antigen presenting cells, playing a decisive role in the cancer immunity cycle. Indeed, endogenous PRR activation within the tumor microenvironment (TME) has been shown to generate spontaneous antitumor T cell immunity, e.g., cGAS-STING mediated activation of antigen presenting cells after release of DNA from dying tumor cells. Thus, instigating intratumor PRR activation, particularly with the goal of generating Th1-promoting inflammation that stokes endogenous priming of antitumor CD8+ T cells, is a growing area of clinical investigation. This approach is analogous to in situ vaccination, ultimately providing a personalized antitumor response against relevant tumor associated antigens. Here I discuss clinical stage intratumor modalities that function via activation of PRRs. These approaches are being tested in various solid tumor contexts including melanoma, colorectal cancer, glioblastoma, head and neck squamous cell carcinoma, bladder cancer, and pancreatic cancer. Their mechanism (s) of action relative to other immunotherapy approaches (e.g., antigen-defined cancer vaccines, CAR T cells, dendritic cell vaccines, and immune checkpoint blockade), as well as their potential to complement these approaches are also discussed. Examples to be reviewed include TLR agonists, STING agonists, RIG-I agonists, and attenuated or engineered viruses and bacterium. I also review common key requirements for effective in situ immune activation, discuss differences between various strategies inclusive of mechanisms that may ultimately limit or preclude antitumor efficacy, and provide a summary of relevant clinical data.

Duke Scholars

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Published In

Cancer Treat Res

DOI

ISSN

0927-3042

Publication Date

2022

Volume

183

Start / End Page

91 / 129

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Receptors, Pattern Recognition
  • Neoplasms
  • Immunotherapy
  • Humans
  • Cancer Vaccines
  • CD8-Positive T-Lymphocytes
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
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ICMJE
MLA
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Brown, M. (2022). Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity. Cancer Treat Res, 183, 91–129. https://doi.org/10.1007/978-3-030-96376-7_3
Brown, Michael. “Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity.Cancer Treat Res 183 (2022): 91–129. https://doi.org/10.1007/978-3-030-96376-7_3.
Brown, Michael. “Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity.Cancer Treat Res, vol. 183, 2022, pp. 91–129. Pubmed, doi:10.1007/978-3-030-96376-7_3.

Published In

Cancer Treat Res

DOI

ISSN

0927-3042

Publication Date

2022

Volume

183

Start / End Page

91 / 129

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Receptors, Pattern Recognition
  • Neoplasms
  • Immunotherapy
  • Humans
  • Cancer Vaccines
  • CD8-Positive T-Lymphocytes
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis