Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses
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Neoantigens sensitize melanomas to checkpoint blockade and trigger epitope spreading to self-antigens, a process mimicked by combination immunotherapy.
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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).”
From Targeting TBK1 to overcome resistance to cancer immunotherapy (2023) · cites this paper as [17]
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Epitope Spreading and the Efficacy of Immune Checkpoint Inhibition in Cancer
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Cancer Therapy-induced Dermatotoxicity as a Window to Understanding Skin Immunity
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Immune Checkpoint Inhibition-related Neuroinflammation Disrupts Cognitive FunctionPreprint
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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.
- ORCID
- Lo, Jennifer A.
- Juneja, Vikram R.
- Su, Mack Y.
- Erlich, Tal H.
- LaFleur, Martin W.
- Kemeny, Lajos V.
- Rashid, Mamunur
- Malehmir, Mohsen
- Rabi, S. Alireza
- Raghavan, Rumya
- Allouche, Jennifer
- Frederick, Dennie T.
- Pauken, Kristen E.
- Weng, Qing Yu
- Pereira da Silva, Marcelo
- Xu, Yu
- Silkworth, Whitney
- Roider, Elisabeth
- Browne, Edward P.
- Lieb, David J.
- Wang, Belinda
- Garraway, Levi A.
- Wu, Catherine J.
- Flaherty, Keith T.
- Mullins, David W.
- Adams, David J.
- Hacohen, Nir
- Hoang, Mai P.
- 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
- PMC
- PMC8130008
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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