Cancer vaccination drives Nanog-dependent evolution of tumor cells towards an immune-resistant and stem-like phenotype
Menée à l'aide d'un modèle murin, cette étude met en évidence le rôle joué par le facteur de transcription Nanog dans l'évolution des cellules tumorales en réponse à une immunothérapie
Due to the exquisite specificity and potency of the immune system, vaccination is in theory the most precise and powerful approach for controlling cancer. However, current data from clinical trials indicate that vaccination rarely yields significant benefits for cancer patients in terms of tumor progression and long-term survival. The poor clinical outcomes of vaccination are primarily caused by mechanisms of immune tolerance, especially within the tumor microenvironment. Here we report that vaccination drives the evolution of tumor cells towards an immune-resistant and stem-like phenotype that promotes tumor growth and nullifies the cytotoxic T lymphocyte (CTL) response. The emergence of this phenotype required the transcription factor Nanog, which is induced as a consequence of immune selection. Nanog expression enhanced the stem-like features of tumor cells and protected them from killing by tumor-reactive CTLs. Delivery of siNanog into tumor-bearing mice rendered the tumor vulnerable to immune surveillance and strongly suppressed its growth. Together, our findings demonstrate tumor adaptation to vaccination through gain of an immune-resistant, stem-like phenotype and identify Nanog as a central molecular target in this process. Future vaccination technology should consider Nanog an important target to enhance the immunotherapeutic response.