Progress in research on the use of induced pluripotent stem cells in tumor prevention, therapy, and tumor modeling
Abstract
Induced pluripotent stem cell technology holds great promise for cancer research and immunotherapy. iPSCs possess pluripotency and unlimited self-renewal capacity, enabling their differentiation into various functional immune effector cells such as T cells, natural killer cells, and macrophages (Macs). Genetically engineered iPSC-derived immune cells have been shown to efficiently and specifically eliminate cancer cells in preclinical studies, and their safety and preliminary efficacy are currently being evaluated in early clinical trials. Although iPSC technology is a relatively recent development, it can be applied in a variety of ways to tackle biological challenges such as tumor heterogeneity, metastasis, and therapeutic resistance. Recent evidence has demonstrated the potential of iPSC-based tumor vaccines, which can leverage the shared transcriptomic characteristics and tumor-associated antigens of iPSCs and cancer cells, to activate CD8 + T cells, induce immune memory formation, and inhibit tumor growth. Moreover, iPSCs can be reprogrammed into cancer stem cell-like cells (CSC-like cells) by tumor microenvironmental cues or genetic mechanism, while cancer cells can be reprogrammed to cancer-derived iPSCs. These complementary approaches provide powerful platforms for modeling tumor initiation, investigating drug resistance mechanisms, and reversing malignant phenotypes. In this review, we discuss new applications of iPSCs in cancer immunotherapy, tumor vaccine development, and CSC-based disease modeling. The review concludes by examining some of the challenges facing the clinical translation of iPSCs, including tumorigenicity risks, low reprogramming efficiency, and the immunosuppressive tumor microenvironment. We also recommend possible solutions to these challenges, which can help to further advance the application of iPSCs in precision oncology and personalized cancer treatment.