Immunotherapy is revolutionizing the treatment of cancer, and the current immunotherapeutics have remarkably improved the outcomes for some cancer patients. However, we still need answers for patients with immunologically cold tumors that do not benefit from the current immunotherapy treatments. Here, we suggest a novel strategy that is based on using a very old and sophisticated system for cancer immunotherapy, namely “intrinsic cancer vaccination”, which seeks to awaken our own immune system to activate tumor-specific T cells. To do this, we must take advantage of the genetic instability of cancer cells and the expression of cancer cell neoantigens to trigger immunity against cancer cells. It will be necessary to not only enhance the phagocytosis of cancer cells by antigen presenting cells but also induce immunogenic cancer cell death and the subsequent immunogenic clearance, cross-priming and generation of tumor-specific T cells. This strategy will allow us to avoid using known tumor-specific antigens, ex vivo manipulation or adoptive cell therapy; rather, we will efficiently present cancer cell neoantigens to our immune system and propagate the cancer-immunity cycle. This strategy simply follows the natural cycle of cancer-immunity from its very first step, and therefore could be combined with any other treatment modality to yield enhanced efficacy.

免疫疗法正在彻底改变癌症的治疗方法，目前的免疫疗法已显着改善了某些癌症患者的预后。但是，对于仍无法从当前的免疫疗法中受益的具有免疫学上寒冷的肿瘤的患者，我们仍然需要答案。在这里，我们提出了一种新的策略，该策略基于使用非常古老且复杂的系统进行癌症免疫治疗，即“内在性癌症疫苗接种”，旨在唤醒我们自己的免疫系统以激活肿瘤特异性T细胞。为此，我们必须利用癌细胞的遗传不稳定性和癌细胞新抗原的表达来触发针对癌细胞的免疫力。不仅需要增强抗原呈递细胞对癌细胞的吞噬作用，而且还需要诱导免疫原性癌细胞死亡以及随后的免疫原性清除，交叉引发和肿瘤特异性T细胞的产生。这种策略将使我们避免使用已知的肿瘤特异性抗原，离体操作或过继性细胞疗法；相反，我们将有效地将癌细胞新抗原呈递给我们的免疫系统，并传播癌症-免疫周期。该策略从一开始就完全遵循癌症免疫力的自然周期，因此可以与任何其他治疗方式结合使用以产生更高的疗效。