文章：

针对已确诊癌症的疫苗：克服免疫逃避带来的挑战

Vaccines for established cancer: overcoming the challenges posed by immune evasion

原文发布日期：2016-03-11

DOI: 10.1038/nrc.2016.16

类型: Review Article

开放获取: 否

要点：

1. Therapeutic vaccines for the induction of tumour-specific T cell responses show high immunogenicity and clinical efficacy over different formulation platforms in pre-cancers but not in established cancers.
2. Cancer vaccines fail to treat established disease owing to a lack of appropriate co-treatment for the immune evasion mechanisms that are operational in the target group.
3. Recognition of escaped tumours with defective major histocompatibility complex (MHC) class I processing and presentation can, in most cases, be restored or induced by activation of CD8⁺ T cells specific for T cell epitopes associated with impaired peptide processing (TEIPP) antigens.
4. The potency of peptide-based vaccines to stimulate type 1 T helper (T_H1) cells and CD8⁺ T cells will be improved by coupling them with pattern recognition receptor (PRR) agonists and by the formation of supramolecular peptide conjugates.
5. The combination of vaccines with therapies that target immune-suppressive myeloid cells, prevent immune checkpoint activation and stimulate local immune cell infiltration will maximize clinical benefit.
6. Future research will focus on methods to quickly assess the most important immunological hurdles present in a patient's tumour so that the best cancer vaccine combination therapy can be given.

要点翻译：

1. 用于诱导肿瘤特异性T细胞反应的治疗性疫苗在癌前病变中显示出高度免疫原性和临床疗效，但在已形成的癌症中效果不佳。
2. 癌症疫苗无法治疗已形成的癌症，原因是缺乏针对目标群体中存在的免疫逃逸机制的适当联合治疗。
3. 在大多数情况下，通过激活针对肽处理受损相关抗原（TEIPP）特异性CD8+T细胞，可以恢复或诱导对主要组织相容性复合体（MHC）I类处理和呈递缺陷的逃逸肿瘤的识别。
4. 通过将肽类疫苗与模式识别受体（PRR）激动剂偶联并形成超分子肽缀合物，可增强其刺激1型辅助T细胞（TH1）和CD8+T细胞的能力。
5. 将疫苗与靶向免疫抑制性髓系细胞、阻止免疫检查点激活及刺激局部免疫细胞浸润的疗法相结合，将最大化临床获益。
6. 未来研究将聚焦于快速评估患者肿瘤中存在的关键免疫学障碍的方法，以便实施最佳的癌症疫苗联合治疗。

英文摘要：

Therapeutic vaccines preferentially stimulate T cells against tumour-specific epitopes that are created by DNA mutations or oncogenic viruses. In the setting of premalignant disease, carcinoma in situ or minimal residual disease, therapeutic vaccination can be clinically successful as monotherapy; however, in established cancers, therapeutic vaccines will require co-treatments to overcome immune evasion and to become fully effective. In this Review, we discuss the progress that has been made in overcoming immune evasion controlled by tumour cell-intrinsic factors and the tumour microenvironment. We summarize how therapeutic benefit can be maximized in patients with established cancers by improving vaccine design and by using vaccines to increase the effects of standard chemotherapies, to establish and/or maintain tumour-specific T cells that are re-energized by checkpoint blockade and other therapies, and to sustain the antitumour response of adoptively transferred T cells.

摘要翻译： 

治疗性疫苗优先刺激T细胞识别由DNA突变或致癌病毒产生的肿瘤特异性表位。在癌前病变、原位癌或微小残留病灶的情况下，治疗性疫苗单药即可取得临床成功；然而，在已形成的癌症中，治疗性疫苗需联合其他治疗以克服免疫逃逸，才能充分发挥疗效。本文综述了在克服由肿瘤细胞内在因素和肿瘤微环境介导的免疫逃逸方面取得的进展。我们总结了如何通过优化疫苗设计，以及利用疫苗增强标准化疗效果、建立和/或维持可被免疫检查点抑制剂及其他疗法重新激活的肿瘤特异性T细胞，并延长过继转移T细胞的抗肿瘤应答，从而在已确诊癌症患者中最大化治疗获益。

原文链接：

Vaccines for established cancer: overcoming the challenges posed by immune evasion