体内检测免疫原性细胞死亡的方法。
Methods to Detect Immunogenic Cell Death In Vivo.
作者信息
Yamazaki Takahiro, Buqué Aitziber, Rybstein Marissa, Chen Jonathan, Sato Ai, Galluzzi Lorenzo
机构信息
Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, New York, NY, USA.
出版信息
Methods Mol Biol. 2020;2055:433-452. doi: 10.1007/978-1-4939-9773-2_20.
In response to selected stressors, cancer cells can undergo a form of regulated cell death that-in immunocompetent syngeneic hosts-is capable of eliciting an adaptive immune response specific for dead cell-associated antigens. Thus, such variant of regulated cell death manifests with robust antigenicity and adjuvanticity. As compared to their normal counterparts, malignant cells are highly antigenic per se, implying that they express a variety of antigens that are not covered by central tolerance. However, the precise modality through which cancer cells die in response to stress has a major influence on adjuvanticity. Moreover, the adjuvanticity threshold to productively drive anticancer immune responses is considerably lower in tumor-naïve hosts as compared to their tumor-bearing counterparts, largely reflecting the establishment of peripheral tolerance to malignant lesions in the latter (but not in the former). So far, no cellular biomarker or combination thereof has been found to reliably predict the ability of cancer cell death to initiate antitumor immunity. Thus, although some surrogate biomarkers of adjuvanticity can be used for screening purposes, the occurrence of bona fide immunogenic cell death (ICD) can only be ascertained in vivo. Here, we describe two methods that can be harnessed to straightforwardly determine the immunogenicity of mouse cancer cells succumbing to stress in both tumor-naïve and tumor-bearing hosts.
针对特定应激源,癌细胞可经历一种程序性细胞死亡形式,在免疫功能正常的同基因宿主中,这种细胞死亡能够引发针对与死亡细胞相关抗原的适应性免疫反应。因此,这种程序性细胞死亡变体具有强大的抗原性和佐剂性。与正常细胞相比,恶性细胞本身具有高度抗原性,这意味着它们表达多种未被中枢耐受覆盖的抗原。然而,癌细胞在应激反应中死亡的精确方式对佐剂性有重大影响。此外,与荷瘤宿主相比,在未接触过肿瘤的宿主中,有效驱动抗癌免疫反应的佐剂性阈值要低得多,这在很大程度上反映了后者(而非前者)对恶性病变建立了外周耐受。到目前为止,尚未发现可靠预测癌细胞死亡引发抗肿瘤免疫能力的细胞生物标志物或其组合。因此,尽管一些佐剂性替代生物标志物可用于筛选目的,但真正的免疫原性细胞死亡(ICD)的发生只能在体内确定。在此,我们描述了两种方法,可用于直接确定在未接触过肿瘤和荷瘤宿主中因应激而死亡的小鼠癌细胞的免疫原性。