Modern cancer therapies often involve the combination of tumor-directed cytotoxic strategies and generation of a host antitumor immune response. The latter is unleashed by immunotherapies that activate the immune system generating a more immunostimulatory tumor microenvironment and a stronger tumor antigen-specific immune response. Studying the interaction between antitumor cytotoxic therapies, dying cancer cells, and the innate and adaptive immune system requires appropriate experimental tumor models in mice. In this review, we discuss the immunostimulatory and immunosuppressive properties of cancer cell lines commonly used in immunogenic cell death (ICD) studies being apoptosis or necroptosis. We will especially focus on the antigenic component of immunogenicity. While in several cancer cell lines the epitopes of endogenously expressed tumor antigens are known, these intrinsic epitopes are rarely determined in experimental apoptotic or necroptotic ICD settings. Instead by far the most ICD research studies investigate the antigenic response against exogenously expressed model antigens such as ovalbumin or retroviral epitopes (e.g., AH1). In this review, we will argue that the immune response against endogenous tumor antigens and the immunopeptidome profile of cancer cell lines affect the eventual biological readouts in the typical prophylactic tumor vaccination type of experiments used in ICD research, and we will propose additional methods involving immunopeptidome profiling, major histocompatibility complex molecule expression, and identification of tumor-infiltrating immune cells to document intrinsic immunogenicity following different cell death modalities.

现代癌症治疗通常涉及肿瘤定向细胞毒性策略和宿主抗肿瘤免疫反应的产生。后者由激活免疫系统的免疫疗法释放，从而产生更具免疫刺激性的肿瘤微环境和更强的肿瘤抗原特异性免疫反应。研究抗肿瘤细胞毒性疗法、垂死的癌细胞以及先天性和适应性免疫系统之间的相互作用需要适当的小鼠实验性肿瘤模型。在这篇综述中，我们讨论了免疫原性细胞死亡 (ICD) 研究中常用的癌细胞系的免疫刺激和免疫抑制特性，即细胞凋亡或坏死性凋亡。我们将特别关注免疫原性的抗原成分。虽然在几种癌细胞系中，内源性表达的肿瘤抗原的表位是已知的，但这些内在表位很少在实验性凋亡或坏死性 ICD 环境中确定。相反，到目前为止，大多数 ICD 研究调查了针对外源表达模型抗原（如卵清蛋白或逆转录病毒表位（例如 AH1））的抗原反应。在这篇综述中，我们将论证针对内源性肿瘤抗原的免疫反应和癌细胞系的免疫肽组概况会影响 ICD 研究中使用的典型预防性肿瘤疫苗接种类型实验的最终生物学读数，我们将提出涉及免疫肽组的其他方法分析，主要组织相容性复合物分子表达，