Prdm1-KO Mouse

Prdm1, also known as BLIMP1, is a transcription factor with diverse functions. It is involved in cell differentiation, immune regulation, and is associated with multiple biological pathways. Prdm1 is crucial for terminal effector cell differentiation in both B and T cells. In B cells, it acts as a master regulator of plasma cell differentiation, while in T cells, it is important for the differentiation of most terminal effector cells [2].

Genetic ablation of Prdm1 in antitumor T cells, such as chimeric antigen receptor (CAR)-engineered T cells, T-cell receptor-engineered T cells, and tumor-infiltrating lymphocytes, enhances the maintenance of an early memory phenotype and polyfunctional cytokine secretion. This promotes the expansion of less differentiated memory CAR-T cells in vivo, leading to improved T-cell persistence and therapeutic efficacy in multiple tumor models [1]. In liver Group 1 innate lymphoid cells (ILCs), Prdm1 positively regulates cancer immune surveillance. Using an Ncr1-driven conditional knockout mouse model, it was found that Prdm1 shapes the composition and maturation of cNK cells. Although it does not affect the killing function of cNK cells, Prdm1-deficient mice show increased cancer metastasis, and Prdm1-deficient cNK cells and liver ILC1s have decreased secretion of interferon-γ, granzyme B, and perforin [3].

In conclusion, Prdm1 is essential for cell differentiation and immune regulation. Studies using Prdm1 knockout or conditional knockout mouse models have revealed its significant roles in cancer-related immune processes, including antitumor T-cell function and liver ILC-mediated cancer immune surveillance, providing insights into potential immunotherapy strategies for cancer treatment.

References:

1. Yoshikawa, Toshiaki, Wu, Zhiwen, Inoue, Satoshi, Suzuki, Shiro, Kagoya, Yuki. . Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy. In Blood, 139, 2156-2172. doi:10.1182/blood.2021012714. https://pubmed.ncbi.nlm.nih.gov/34861037/

2. Boi, Michela, Zucca, Emanuele, Inghirami, Giorgio, Bertoni, Francesco. 2014. PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas. In Leukemia & lymphoma, 56, 1223-8. doi:10.3109/10428194.2014.953155. https://pubmed.ncbi.nlm.nih.gov/25115512/

3. He, Jitian, Gao, Le, Wang, Peiying, Yang, Zhouxin, Wang, Youwei. 2024. Prdm1 positively regulates liver Group 1 ILCs cancer immune surveillance and preserves functional heterogeneity. In eLife, 13, . doi:10.7554/eLife.92948. https://pubmed.ncbi.nlm.nih.gov/39133873/