Cited by 97Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

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Lo, Jennifer A., Kawakubo, Masayoshi, Juneja, Vikram R., Su, Mack Y., Erlich, Tal H., LaFleur, Martin W., Kemeny, Lajos V., Rashid, Mamunur +29 more·2021·Science Translational Medicine

Abstract

Neoantigens sensitize melanomas to checkpoint blockade and trigger epitope spreading to self-antigens, a process mimicked by combination immunotherapy.

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Crossref · 10.1126/scitranslmed.abd8636

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  • TBK1i could overcome primary (intrinsic) resistance in MDOTS derived from anti-PD-1 resistant D4M.3A tumours.

    “Ex vivo profiling of MDOTS derived from anti-PD-1 resistant D4M.3A (Braf-mutant/Pten-null) tumours 17 showed that TBK1i could overcome primary (intrinsic) resistance using a separate autochthonous murine melanoma model (Fig. 1f).”

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  1. [27]Fuertes MB, Kacha AK, Kline J, Woo S-R, Kranz DM, Murphy KM, Gajewski TF, Host type I IFN signals are required for antitumor CD8 +T cell responses through CD8α +dendritic cells, J. Exp. Med 208, 2005– 2016 (2011). 21930765 PMC3182064

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Authors
Lo, J. A., Kawakubo, M., Juneja, V. R., Su, M. Y., Erlich, T. H., LaFleur, M. W., Kemeny, L. V., Rashid, M., Malehmir, M., Rabi, S. A., Raghavan, R., Allouche, J., Kasumova, G., Frederick, D. T., Pauken, K. E., Weng, Q. Y., Pereira da Silva, M., Xu, Y., van der Sande, A. A. J., Silkworth, W., Roider, E., Browne, E. P., Lieb, D. J., Wang, B., Garraway, L. A., Wu, C. J., Flaherty, K. T., Brinckerhoff, C. E., Mullins, D. W., Adams, D. J., Hacohen, N., Hoang, M. P., Boland, G. M., Freeman, G. J., Sharpe, A. H., Manstein, D., & Fisher, D. E.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
  • Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Wellcome Trust (GB)
  • Broad Institute (US)
  • Stanford University (US)
  • University of North Carolina at Chapel Hill (US)
  • Massachusetts General Hospital (US)
  • Dartmouth College (US)
Corresponding author
  • Kawakubo, Masayoshi
  • Juneja, Vikram R.
  • Su, Mack Y.
  • Erlich, Tal H.
  • Boland, Genevieve M.
  • Freeman, Gordon J.
  • Sharpe, Arlene H.
  • Manstein, Dieter
  • Fisher, David E.
Venue
Science Translational Medicine
Published
2021-02-17
Volume
13
Issue
581
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
OpenAlex
W3129494031
Cited by
97
References
44
Citations by year
2026: 7 · 2025: 23 · 2024: 18 · 2023: 12 · 2022: 17 · 2021: 20
FWCI
6.10
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health (P01 AI056299)
  • National Cancer Institute (P50CA101942, P50CA206963)
  • Cancer Research Institute
  • Leukemia and Lymphoma Society
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Cancer Research UK
  • Swiss National Science Foundation
  • Dr. Mildred Scheel Stiftung für Krebsforschung
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
epitope spreading, immune checkpoint blockade, anti-PD-1 therapy, melanoma, neoantigens, fractional photothermolysis, imiquimod, tumor immunogenicity, pancreatic ductal adenocarcinoma
MeSH terms
Immune Checkpoint Inhibitors, Animals, Epitopes, Antigens, Neoplasm, Humans, Melanocytes, Melanoma, Mice

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