Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy.
Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy.
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DOI：
10.1126/sciadv.abj3671
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发表时间：
2022-01-28
期刊：
影响因子：
13.6
通讯作者：
Depil S
中科院分区：
文献类型：
--
作者：
Bonaventura P;Alcazer V;Mutez V;Tonon L;Martin J;Chuvin N;Michel E;Boulos RE;Estornes Y;Valladeau-Guilemond J;Viari A;Wang Q;Caux C;Depil S
人类内源性逆转录病毒（HERV）占人类基因组的8%。HERV产品可能代表与癌症免疫治疗相关的肿瘤抗原。我们开发了一种生物信息学方法来鉴定实体瘤中源自癌症相关HERV的共享CD 8 + T细胞表位。在具有翻译证据的最常见的HLA-A2表位中选择六个候选者进行免疫学评价。体外引发试验证实了这些表位的免疫原性，其诱导高亲和力的CD 8 + T细胞克隆。这些T细胞特异性地识别并杀死在HLA分子上呈递HERV表位的HLA-A2+肿瘤细胞，如通过质谱所证明的。此外，表位特异性的CD 8 + T细胞中鉴定的Dextramer染色肿瘤浸润淋巴细胞HLA-A2+乳腺癌患者。最后，我们发现HERV特异性T细胞裂解患者来源的类器官。这些共享的病毒样表位对于癌症疫苗或基于T细胞的免疫疗法的开发具有重大意义，特别是在具有低/中等突变负荷的肿瘤中。生物信息学方法鉴定来自HERV的肿瘤表位，其诱导对肿瘤细胞具有细胞毒性的高亲合力CD 8 + T细胞。
Human endogenous retroviruses (HERVs) represent 8% of the human genome. HERV products may represent tumor antigens relevant for cancer immunotherapy. We developed a bioinformatic approach to identify shared CD8+ T cell epitopes derived from cancer-associated HERVs in solid tumors. Six candidates among the most commonly shared HLA-A2 epitopes with evidence of translation were selected for immunological evaluation. In vitro priming assays confirmed the immunogenicity of these epitopes, which induced high-avidity CD8+ T cell clones. These T cells specifically recognize and kill HLA-A2+ tumor cells presenting HERV epitopes on HLA molecules, as demonstrated by mass spectrometry. Furthermore, epitope-specific CD8+ T cells were identified by dextramer staining among tumor-infiltrating lymphocytes from HLA-A2+ patients with breast cancer. Last, we showed that HERV-specific T cells lyse patient-derived organoids. These shared virus-like epitopes are of major interest for the development of cancer vaccines or T cell–based immunotherapies, especially in tumors with low/intermediate mutational burden. A bioinformatic approach identifies tumor epitopes from HERVs inducing high-avidity CD8+ T cells cytotoxic against tumor cells.
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影响因子：
30.8
作者：
Jang, Hyo Sik;Shah, Nakul M.;Wang, Ting
通讯作者：
Wang, Ting
影响因子：
16.6
作者：
Bobisse S;Genolet R;Roberti A;Tanyi JL;Racle J;Stevenson BJ;Iseli C;Michel A;Le Bitoux MA;Guillaume P;Schmidt J;Bianchi V;Dangaj D;Fenwick C;Derré L;Xenarios I;Michielin O;Romero P;Monos DS;Zoete V;Gfeller D;Kandalaft LE;Coukos G;Harari A
通讯作者：
Harari A
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
DOI：
10.1158/1078-0432.ccr-14-3197
发表时间：
2015-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Krishnamurthy J;Rabinovich BA;Mi T;Switzer KC;Olivares S;Maiti SN;Plummer JB;Singh H;Kumaresan PR;Huls HM;Wang-Johanning F;Cooper LJ
通讯作者：
Cooper LJ
DOI：
10.1126/science.abc8697
发表时间：
2021-03-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hsiue EH;Wright KM;Douglass J;Hwang MS;Mog BJ;Pearlman AH;Paul S;DiNapoli SR;Konig MF;Wang Q;Schaefer A;Miller MS;Skora AD;Azurmendi PA;Murphy MB;Liu Q;Watson E;Li Y;Pardoll DM;Bettegowda C;Papadopoulos N;Kinzler KW;Vogelstein B;Gabelli SB;Zhou S
通讯作者：
Zhou S