Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors
Abigail L. Sedlacek, … , Ion I. Mandoiu, Robert J. Binder
Abigail L. Sedlacek, … , Ion I. Mandoiu, Robert J. Binder
Published April 4, 2019
Citation Information: JCI Insight. 2019;4(7):e127239. https://doi.org/10.1172/jci.insight.127239.
View: Text | PDF
Research Article Immunology

CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors

  • Text
  • PDF
Abstract

The immune system detects aberrant, premalignant cells and eliminates them before the development of cancer. Immune cells, including T cells, have been shown to be critical components in eradicating these aberrant cells, and when absent in the host, incidence of cancer increases. Here, we show that CD91, a receptor expressed on antigen-presenting cells, is required for priming immune responses to nascent, emerging tumors. In the absence of CD91, effector immune responses are subdued, and tumor incidence and progression are amplified. We also show that, consequently, tumors that arise in the absence of CD91 express neo-epitopes with indices that are indicative of greater immunogenicity. Polymorphisms in human CD91 that are expected to affect ligand binding are shown to influence antitumor immune responses in cancer patients. This study presents a molecular mechanism for priming immune responses to nascent, emerging tumors that becomes a predictor of cancer susceptibility and progression.

Authors

Abigail L. Sedlacek, Theodore P. Younker, Yu Jerry Zhou, Lisa Borghesi, Tatiana Shcheglova, Ion I. Mandoiu, Robert J. Binder

×

Figure 3

CD91-mediated immunity to nascent tumors is fixated on neo-epitopes with high differential aggretope index.

Options: View larger image (or click on image) Download as PowerPoint
CD91-mediated immunity to nascent tumors is fixated on neo-epitopes with...
Tumors induced with MCA in CD91fl/flCD11cCre and CD91fl/fl mice were harvested and analyzed by whole-exome sequencing. (A) Total number of all SNVs derived from tumors in either group. (B) The total number of 8-, 9-, 10-, and 11-mer–mutated peptides spanning the mutation and predicted from each SNV. (C–E) The number of mutated peptides with the indicated half maximal inhibitory concentration (IC50) threshold. (F) The average differential aggretope index (DAI), which measures the differential binding affinity between the WT and corresponding mutated peptides, derived from all mutated peptides for the H-2-Kb or H-2-Db MHC allele. (G) The average DAI for only mutated peptides with high affinity for H-2-Kb or H-2-Db MHC binding (IC50 < 500). The box plots depict the minimum and maximum values (whiskers), the upper and lower quartiles, and the median. The length of the box represents the interquartile range. (H and I) The number of peptides with indicated maximum DAI for H-2b (H) or H-2d (I). Statistical significance was determined by Student’s 2-tailed t test. *P < 0.05.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts