Abstract:
:Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and expanding a single-cell clone, we generated a mutagenized model that exhibits high somatic mutation burden. When inoculated at low cell numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (Yale University Mouse Melanoma Exposed to Radiation) regresses after a brief period of growth. This regression phenotype is dependent on T cells as YUMMER1.7 tumors grow significantly faster in immunodeficient Rag1-/- mice and C57BL/6J mice depleted of CD4 and CD8 T cells. Interestingly, regression can be overcome by injecting higher cell numbers of YUMMER1.7, which results in tumors that grow without effective rejection. Mice that have previously rejected YUMMER1.7 tumors develop immunity against higher doses of YUMMER1.7 tumor challenge. In addition, escaping YUMMER1.7 tumors are sensitive to anti-CTLA-4 and anti-PD-1 therapy, establishing a new model for the evaluation of immune checkpoint inhibition and antitumor immune responses.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Wang J,Perry CJ,Meeth K,Thakral D,Damsky W,Micevic G,Kaech S,Blenman K,Bosenberg Mdoi
10.1111/pcmr.12591subject
Has Abstractpub_date
2017-07-01 00:00:00pages
428-435issue
4eissn
1755-1471issn
1755-148Xjournal_volume
30pub_type
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
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journal_title:Pigment cell & melanoma research
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更新日期:2010-12-01 00:00:00
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journal_title:Pigment cell & melanoma research
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