Rejection of immunogenic tumor clones is limited by clonal fraction Journal Article


Authors: Gejman, R. S.; Chang, A. Y.; Jones, H. F.; DiKun, K.; Hakimi, A. A.; Schietinger, A.; Scheinberg, D. A.
Article Title: Rejection of immunogenic tumor clones is limited by clonal fraction
Abstract: Tumors often co-exist with T cells that recognize somatically mutated peptides presented by cancer cells on major histocompatibility complex I (MHC-I). However, it is unknown why the immune system fails to eliminate immune-recognizable neoplasms before they manifest as frank disease. To understand the determinants of MHC-I peptide immunogenicity in nascent tumors, we tested the ability of thousands of MHC-I ligands to cause tumor subclone rejection in immunocompetent mice by use of a new 'PresentER' antigen presentation platform. Surprisingly, we show that immunogenic tumor antigens do not lead to immune-mediated cell rejection when the fraction of cells bearing each antigen ('clonal fraction') is low. Moreover, the clonal fraction necessary to lead to rejection of immunogenic tumor subclones depends on the antigen. These data indicate that tumor neoantigen heterogeneity has an underappreciated impact on immune elimination of cancer cells and has implications for the design of immunotherapeutics such as cancer vaccines. © 2018, Gejman et al.
Keywords: mouse; tumor antigens; genetic heterogeneity; cancer immunology; cancer biology; tumor evolution; tumor resistance to immune response
Journal Title: eLife
Volume: 7
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2018-11-30
Start Page: e41090
Language: English
DOI: 10.7554/eLife.41090
PROVIDER: scopus c2 - 30499773
PMCID: PMC6269121
PUBMED: 30499773
DOI/URL:
Notes: Elife -- Export Date: 2 January 2019 -- Article -- Source: Scopus C2 - 30499773
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MSK Authors
  1. Abraham Ari Hakimi
    127 Hakimi
  2. Ron Shlomo Gejman
    8 Gejman
  3. Aaron   Chang
    10 Chang
  4. Krysta Marie Dikun
    1 Dikun
  5. Heather Frances Jones
    1 Jones