Deregulation of antigen presentation is a common cancer feature that leads to immune escape. A new study reports an approach to reprogramme tumour cells in vivo, enabling them to present antigens, establish systemic immunity and induce tumour regression.

Using adenoviral delivery of the transcription factors PU.1, IRF8 and BATF3, Ascic et al. reprogrammed mouse tumour cells into type 1 conventional dendritic (cDC1)-like cells. In mouse melanoma models, reprogrammed tumour cells presented antigens similar to cDC1s and induced tumour regression. The authors found that reprogrammed tumour cells caused the formation of dense lymphocyte clusters resembling tertiary lymphoid structures, enhanced the infiltration of memory and stem-like T cells, and induced polyclonal cytotoxic and memory T cell responses. Moreover, the researchers showed that using the same transcription factors could induce a cDC1-like phenotype with enhanced immunogenicity in human xenograft models. Finally, several experiments, including in spheroids, revealed that cDC1 reprogramming and cytotoxicity induction within the human tumour microenvironment was unaffected by immunosuppression.

抗原呈递失调是导致免疫逃逸的常见癌症特征。一项新研究报告了一种在体内重编程肿瘤细胞的方法，使它们能够呈递抗原、建立全身免疫并诱导肿瘤消退。

利用转录因子 PU.1、IRF8 和 BATF3 的腺病毒递送，Ascic 等人将小鼠肿瘤细胞重编程为 1 型常规树突状 （cDC1） 样细胞。在小鼠黑色素瘤模型中，重编程的肿瘤细胞呈递类似于 cDC1 的抗原并诱导肿瘤消退。作者发现，重编程的肿瘤细胞导致形成类似于三级淋巴结构的致密淋巴细胞簇，增强记忆和干细胞样 T 细胞的浸润，并诱导多克隆细胞毒性和记忆 T 细胞反应。此外，研究人员表明，使用相同的转录因子可以在人类异种移植模型中诱导具有增强免疫原性的 cDC1 样表型。最后，包括球状体在内的几项实验表明，人类肿瘤微环境中的 cDC1 重编程和细胞毒性诱导不受免疫抑制的影响。