Abstract:
:The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities between metastases from the same patient. Furthermore, we reveal that two neoantigen-specific clonotypes killed 90% of autologous melanoma cells, both in vitro and in vivo, showing that a limited set of neoantigen-specific T cells may play a central role in melanoma tumor rejection. Our findings indicate that combining HLA peptidomics with neoantigen predictions allows robust identification of targetable neoantigens, which could successfully guide personalized cancer immunotherapies.Significance: As neoantigen targeting is becoming more established as a powerful therapeutic approach, investigating these molecules has taken center stage. Here, we show that a limited set of neoantigen-specific T cells mediates tumor rejection, suggesting that identifying just a few antigens and their corresponding T-cell clones could guide personalized immunotherapy. Cancer Discov; 8(11); 1366-75. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 1333.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Kalaora S,Wolf Y,Feferman T,Barnea E,Greenstein E,Reshef D,Tirosh I,Reuben A,Patkar S,Levy R,Quinkhardt J,Omokoko T,Qutob N,Golani O,Zhang J,Mao X,Song X,Bernatchez C,Haymaker C,Forget MA,Creasy C,Greenberg P,doi
10.1158/2159-8290.CD-17-1418subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1366-1375issue
11eissn
2159-8274issn
2159-8290pii
2159-8290.CD-17-1418journal_volume
8pub_type
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