Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8⁺ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8⁺ T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.

中文翻译：

---

在免疫治疗初治卵巢癌中灵敏且频繁地鉴定高亲合力新表位特异性 CD8 + T 细胞。


针对源自非同义体细胞突变的私有肿瘤新抗原的免疫疗法是个性化癌症免疫疗法的一种有前途的策略。然而，低突变负荷肿瘤类型的可行性仍然未知。对循环和肿瘤浸润淋巴细胞 (TIL) 的新表位特异性 CD8 ⁺ T 细胞进行全面深入的分析，可以从大多数未接受过免疫治疗的晚期上皮性卵巢癌患者中迅速鉴定出寡克隆和多功能此类细胞。新表位识别在循环 T 细胞和 TIL 之间不一致，并且更有可能在 TIL 中发现，与血液对应物相比，TIL 表现出更高的功能亲合力和具有更高预测亲和力的独特 TCR。我们的结果表明，即使在体细胞突变数量相对较少的肿瘤中，也可以实现新表位特异性 CD8 ⁺ T 细胞的鉴定，并且 TIL 中的新表位验证扩展了针对此类肿瘤进行基于突变组的个性化免疫治疗的机会。