免疫检查点阻断已经彻底改变了癌症治疗方式，并提高了一部分患者的生存率。然而，许多患者并未从免疫疗法中获益，治疗耐药性是一个重要挑战。Kruppel样因子12 (KLF12) 是一种转录抑制剂，其在肿瘤免疫中的作用尚不清楚。通过流式细胞仪在体内和体外证明了KLF12与CD8+ T细胞之间的关系。使用逆转录定量PCR、Western blot、FACS、染色质免疫沉淀-PCR和双荧光素酶报告基因试验等成果，以及应用小干扰RNA (siRNA) 和抑制剂，研究了KLF12调控CD8+ T细胞的作用和潜在机制。在多个小鼠肿瘤模型中进行了体内疗效研究，应用抗程序性细胞死亡蛋白1联合KLF12或半乳糖凝集素-1 (Gal-1) 抑制剂进行实验。本研究发现肿瘤KLF12的表达与免疫疗法耐药性相关。KLF12抑制CD8+ T细胞的体内和体外浸润和功能。机制上，KLF12通过与其启动子结合来抑制Gal-1的表达，从而改善CD8+ T细胞的浸润和功能，对癌症免疫疗法至关重要。本研究发现了一条调控CD8+ T细胞肿瘤内浸润的新途径，针对KLF12/Gal-1轴可能成为免疫疗法耐药患者的新的治疗靶点。© 作者及其雇主（2023）。在CC BY-NC许可下可重新使用。不得进行商业再利用。由BMJ出版。

Immune checkpoint blockade has revolutionized cancer treatment and has improved the survival of a subset of patients with cancer. However, numerous patients do not benefit from immunotherapy, and treatment resistance is a major challenge. Krüppel-like factor 12 (KLF12) is a transcriptional inhibitor whose role in tumor immunity is unclear.We demonstrated a relationship between KLF12 and CD8+ T cells in vivo and in vitro by flow cytometry. The role and underlying mechanism that KLF12 regulates CD8+ T cells were investigated using reverse transcription and quantitative PCR, western blot FACS, chromatin immunoprecipitation-PCR and Dual-Luciferase reporter assays, etc, and employing small interfering RNA (siRNA) and inhibitors. In vivo efficacy studies were conducted with multiple mouse tumor models, employing anti-programmed cell death protein 1 combined with KLF12 or galectin-1 (Gal-1) inhibitor.Here, we found that the expression of tumor KLF12 correlates with immunotherapy resistance. KLF12 suppresses CD8+ T cells infiltration and function in vitro and in vivo. Mechanistically, KLF12 inhibits the expression of Gal-1 by binding with its promoter, thereby improving the infiltration and function of CD8+ T cells, which plays a vital role in cancer immunotherapy.This work identifies a novel pathway regulating CD8+ T-cell intratumoral infiltration, and targeting the KLF12/Gal-1 axis may serve as a novel therapeutic target for patients with immunotherapy resistance.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.