Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
National Clinical Resaerch Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Cancer Commun (Lond). 2024 Jun;44(6):601-636. doi: 10.1002/cac2.12546. Epub 2024 May 7.
Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called "cold" tumors which are unresponsive to immunotherapy, and the opposite are "hot" tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of "cold" tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming "cold" tumors into "hot" tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in "cold" tumor.
自免疫疗法问世以来，癌症治疗取得了重大进展。然而，仍有一些恶性肿瘤患者对免疫治疗没有反应。缺乏免疫原性的肿瘤被称为“冷”肿瘤，对免疫治疗无反应，相反的是“热”肿瘤。免疫抑制细胞（ISCs）是指能够抑制免疫反应的细胞，如肿瘤相关巨噬细胞（TAMs）、髓源性抑制细胞（MDSCs）、调节性 T（Treg）细胞等。ISCs 浸润越多，肿瘤的免疫原性越弱，表现出“冷”肿瘤的特征。ISCs 在肿瘤微环境（TME）中的功能障碍可能在治疗反应不敏感中发挥重要作用。先前的研究发现，表观遗传机制在 ISCs 的调节中起着重要作用。调节 ISCs 可能是将“冷”肿瘤转化为“热”肿瘤的一种新方法。在这里，我们重点关注 ISCs 在 TME 中的功能，并讨论了表观遗传学如何参与调节 ISCs。此外，我们总结了表观遗传药物将免疫治疗不敏感的肿瘤转化为免疫治疗敏感的肿瘤的机制，这将是未来“冷”肿瘤免疫治疗的一个创新趋势。
