DLL1 orchestrates CD8 <sup>+</sup> T cells to induce long-term vascular normalization and tumor regression
Naidong Zhang, Rongping Yin, Pei Zhou, Xiaomei Liu, Peng Fan, Qian Long, Dong Li, Chenglin Zhang, Xichen Zheng, Shengming Deng, Jiajie Kuai, Zhenhua Liu, Wen Jiang, Xiaohua Wang, Depei Wu, Yuhui Huang
Abstract
Significance Cancer immunotherapy demonstrates durable clinical efficacy but only in a small percentage of cancer patients. The aberrant tumor blood vessels and resulting hypoxic tumor microenvironment are major obstacles to hinder cancer immunotherapy. Tumor vascular normalization is a promising strategy to overcome these hindrances; however, the normalizing effects induced by current available approaches are often transient, limiting its therapeutic benefits. Here, we show that Delta-like 1 (DLL1) can induce long-term tumor vascular normalization, alleviate the hypoxia and immunosuppression within the tumor microenvironment, and prolong survival of anti-CTLA4 therapy. This study suggests that DLL1 is a potential target to persistently normalize the tumor microenvironment to enhance cancer immunotherapy.