肿瘤免疫学的谬误：进化压力，病毒作为自然界的遗传工程工具和T细胞监视清除新生自私细胞的出现
The fallacy of tumor immunology: Evolutionary pressures, viruses as nature's genetic engineering tools and T cell surveillance emergence for purging nascent selfish cells
摘要：
美国和匈牙利在1900年和1896年的统计记录显示，在医学取得巨大进步之前，分别有32%和27%的人死于感染，而只有5%和2%的人死于癌症。这些数据可以被解释为意味着（i）免疫系统进化为清除新生的自私细胞，这些自私细胞通过同种异源细胞建立了散布在胞体和种系中的天然嵌合体，以及（ii）对代表异种异源的病原体的防御在进化后期出现。从免疫的语义陷阱和T细胞活化的“双信号”模型的束缚中“解放”T细胞，我们指出了对癌症的免疫反应在概念上不同于对感染的免疫反应的理论依据。我们认为，一个信号模型（随机影响）的解释T细胞活化的优先被广泛接受的双信号模型的共刺激。我们的单信号模型的令人信服的证据来自64.2%接受抗CTLA-4抗体（ipilimumab）治疗的晚期黑色素瘤患者中广泛的自身免疫不良事件，该抗体阻断了免疫检查点。利用T细胞释放出的自身免疫能力可能有助于战胜癌症。假设针对同基因肿瘤的免疫接种也会有效是一个谬误。
英文摘要：
The US and Hungarian statistical records of the years 1900 and 1896, respectively, before the dramatic medical advances, show 32% and 27% deaths attributable to infections, whereas only 5% and 2% due to cancer. These data can be interpreted to mean that (i) the immune system evolved for purging nascent selfish cells, which establish natural chimerism littering the soma and the germline by conspecific alien cells and (ii) defense against pathogens that represent xenogeneic aliens appeared later in evolution. `Liberating' T cells from the semantic trap of immunity and the shackles of the `two-signal' model of T cell activation, we point out theoretical grounds that the immune response to cancer is conceptually different from the immune response to infection. We argue for a one-signal model (with stochastic influences) as the explanation for T cell activation in preference to the widely accepted two-signal model of co-stimulation. Convincing evidence for our one-signal model emerged from the widespread autoimmune adverse events in 64.2% of advanced melanoma patients treated with the anti-CTLA-4 antibody (ipilimumab) that blocks an immune checkpoint. Harnessing the unleashed autoimmune power of T cells could be rewarding to defeat cancer. Assuming that immunization against isogeneic tumors also would be effective is a fallacy.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
