Department of Surgery/Oncology, St Pantelimon Hospital, Carol Davila University, Bucharest, Romania.
Melanoma Res. 2019 Jun;29(3):231-236. doi: 10.1097/CMR.0000000000000573.
Until now, malignancy has been considered a cellular problem represented by the perturbed (uncontrolled) division of the cells associated with invasion and metastasis. Contrary to this classical approach, a new perspective suggests that cancerous disease is, in fact, a supracellular problem represented by inadequate evolution of complex supracellular processes (embryogenesis, development, regeneration, etc.). Such complex processes would be disconnected from the real needs of the body, inducing unnecessary or even dangerous events such as an exacerbated rate of the cell division, angiogenesis, immunosuppression (specific to embryogenesis and melanoma), invasion (mediated by trophoblastic/placental factors in melanoma), and migration (specific to neural crest cells, which generate melanocytes - the most common origin for melanoma). As a result, a correct and comprehensive interpretation of cancer (causes, evolution, therapy, and prevention) should be conducted from a supracellular perspective. After presenting the supracellular perspective, this article further investigates the favorable evolution of malignant melanoma in two distinct situations: in patients receiving no therapy and in patients treated with immune-checkpoint inhibitors. In patients receiving no therapy, spontaneous regressions of melanoma could be the result of several autoimmune reactions (inducing not only melanoma regression but also vitiligo, an autoimmune event frequently associated with melanoma). Patients treated with immune-checkpoint inhibitors develop similar autoimmune reactions, which are clearly correlated with better therapeutic results. The best example is vitiligo, which is considered a positive prognostic factor for patients receiving immune-checkpoint inhibitors. This finding indicates that immune-checkpoint inhibitors induce distinct types of autoimmune events, some corresponding to specific favorable autoimmune mechanisms (favoring tumor regression) and others to common unfavorable adverse reactions (which should be avoided or minimized). In conclusion, the spectrum of autoimmune reactions induced by immune-checkpoint inhibitors should be restricted in the near future to only these specific favorable autoimmune mechanisms. In this way, the unnecessary autoimmune reactions/autoaggressions could be avoided (a better quality of life), and treatment specificity and efficiency should increase (a higher response rate for melanoma therapy).
到目前为止，恶性肿瘤一直被认为是一种细胞问题，表现为与侵袭和转移相关的细胞不受控制的分裂（紊乱）。与这种经典方法相反，一种新的观点表明，癌症实际上是一种超细胞问题，表现为复杂的超细胞过程（胚胎发生、发育、再生等）的进化不足。这种复杂的过程与身体的实际需求脱节，导致不必要甚至危险的事件，如细胞分裂、血管生成、免疫抑制（胚胎发生和黑色素瘤特有的）、侵袭（黑色素瘤中滋养层/胎盘因子介导的）和迁移（神经嵴细胞特有的，产生黑色素细胞——黑色素瘤最常见的起源）的加剧。因此，正确全面地解释癌症（病因、进化、治疗和预防）应该从超细胞的角度进行。在提出超细胞观点之后，本文进一步研究了恶性黑色素瘤在两种不同情况下的有利进化：在未接受治疗的患者和接受免疫检查点抑制剂治疗的患者中。在未接受治疗的患者中，黑色素瘤的自发消退可能是几种自身免疫反应的结果（不仅诱导黑色素瘤消退，还诱导白癜风，这是一种经常与黑色素瘤相关的自身免疫事件）。接受免疫检查点抑制剂治疗的患者会出现类似的自身免疫反应，这与更好的治疗效果明显相关。最好的例子是白癜风，它被认为是接受免疫检查点抑制剂治疗的患者的一个积极预后因素。这一发现表明，免疫检查点抑制剂诱导了不同类型的自身免疫反应，一些反应对应于特定的有利自身免疫机制（有利于肿瘤消退），而另一些反应对应于常见的不利不良反应（应避免或最小化）。总之，免疫检查点抑制剂诱导的自身免疫反应谱在不久的将来应该仅限于这些特定的有利自身免疫机制。通过这种方式，可以避免不必要的自身免疫反应/自身攻击（提高生活质量），并提高治疗的特异性和效率（提高黑色素瘤治疗的反应率）。
