Immune checkpoint inhibitor and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential for cancers with high tumor mutation burden (TMB). Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class I-presented peptides in both melanoma, a hot tumor with high TMB, and EGFR mutant lung adenocarcinoma, a cold tumor with low TMB. We identified several classes of neopeptides, including mutated neoantigens and more than 1000 post-translationally modified peptides representing 58 different PTMs. We constructed a cancer germline (CG) antigen database with 285 antigens and identified 42 Class I-presented CG antigens. Finally, we developed a non-canonical peptide discovery pipeline to identify 44 lncRNA-derived peptides and validated Class I binding for select neopeptides. We provide direct evidence of HLA Class I presentation of a large number of neopeptides for potential vaccine or adoptive cell therapy in melanoma and mutant EGFR lung cancer.

中文翻译：

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蛋白质组学分析揭示了HLA I类在黑色素瘤和EGFR突变型肺腺癌中的免疫肽组

免疫检查点抑制剂和过继淋巴细胞转移疗法已显示出对具有高肿瘤突变负担（TMB）的癌症具有巨大的治疗潜力。在这里，我们采用了基于质谱（MS）的蛋白质组学大规模分析，以鉴定黑色素瘤（一种高TMB的热肿瘤）和EGFR突变型肺腺癌（一种寒冷的肿瘤）中潜在的免疫原性人白细胞抗原（HLA）I类呈递的肽TMB低的肿瘤。我们鉴定了几类新肽，包括突变的新抗原和代表58种不同PTM的1000多种翻译后修饰肽。我们构建了具有285种抗原的癌症生殖系（CG）抗原数据库，并确定了42种I类呈递的CG抗原。最后，我们开发了一种非规范的肽发现管线，以鉴定44种lncRNA衍生的肽，并验证了针对某些新肽的I类结合。我们提供了直接的证据证明HLA I类呈递的大量新肽可用于黑色素瘤和突变型EGFR肺癌的潜在疫苗或过继细胞治疗。