Data from Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma
Year: 2023
Type: other
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
Authors: Shelly Kalaora, Yochai Wolf, Tali Feferman, Eilon Barnea, Erez Greenstein, Dan Reshef, Itay Tirosh, Alexandre Reuben, Sushant Patkar, Ronen Levy, Juliane Quinkhardt, Tana Omokoko, Nouar Qutob, Ofra Golani, Jianhua Zhang, Xizeng Mao, Xingzhi Song, Chantale Bernatchez, Cara Haymaker, Marie-Andrée Forget, Caitlin Creasy, Polina Greenberg, Brett W. Carter, Zachary A. Cooper, Steven A. Rosenberg, Michal Lotem, Ugur Sahin, Guy Shakhar, Eytan Ruppin, Jennifer A. Wargo, Nir Friedman, Arie Admon, Yardena Samuels
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4392689707