Centro di Riferimento Oncologico, Department of Translational Research, Immunopathology and Cancer Biomarkers, 33081 Aviano (PN), Italy.
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi (SA), Italy.
Int J Mol Sci. 2018 Feb 16;19(2):594. doi: 10.3390/ijms19020594.
Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD), is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1). While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC) vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.
免疫原性细胞凋亡,或者更准确地称为免疫原性细胞死亡(ICD),是一种最近描述的细胞凋亡形式,由一组特定的化疗药物或物理治疗方式诱导,如电离辐射和光动力疗法。ICD 的独特特征是能够促进吞噬细胞识别和清除凋亡的肿瘤细胞,并伴随着促炎分子(如细胞因子和高迁移率族蛋白 1)的释放。虽然体外和动物模型表明 ICD 是介导某些抗癌药物临床疗效的分子机制之一,但很难在癌症患者中明确证明其贡献。临床证据表明,单独诱导 ICD 可能不足以完全颠覆肿瘤的免疫抑制微环境。然而,最近研究的有趣结果考虑利用 ICD 来提高癌细胞的免疫原性,将其用作树突状细胞(DC)疫苗中抗原载体。在此,我们讨论了经历 ICD 的癌细胞表达或释放的危险信号对未成熟和成熟 DC 成熟和激活的影响,突出了 ICD 在过继免疫治疗方案中的潜在附加价值。