撰文丨王聪 编辑丨王多鱼 排版丨水成文 结核病 （主要是 肺结核 ） 是全球因传染病导致死亡和残疾的首要原因 （COVID-19 期间除外） ，每年有 120 万人因此死亡。结核病负担在低收入和中等收入 国家尤为沉重，结核病是这些国家所有疾病致病和致死的主要原因，近几十年来几乎没有什么变化。 结核病 由 结核分枝杆菌 感染所致，其 全球疾病负担的部分原因在于缺乏足够有效的结核病疫苗。 实际上，唯一获批的结核病疫苗—— 卡介苗 （BCG） ， 对 儿童结核病的预防效果较高，但在青少年和成年人中效果显著下降，而且，卡介苗的重复接种也未见成效。 因此，开发更有效的结核病疫苗是全球卫生的优先事项。此外，鉴于结核病流行国家儿童早期卡介苗接种率较高，下一代结核病疫苗可能要在卡介苗免疫的背景 下进行接种。 2025 年 9 月 15 日，哈佛大学医学院的研究人员在国际顶尖学术期刊 Cell 上发表了题为： Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines 的研究论文。 该研究通过挖掘人类 CD4 T细胞抗原库，开发了一款 ...

Core Viewpoint - The article discusses the cellular mechanisms underlying the beneficial and detrimental effects of bacterial antitumor immunotherapy, highlighting the importance of injection timing in maximizing therapeutic efficacy and minimizing tumor promotion risks [3][10]. Group 1: Research Findings - The study utilized a non-tumor antigen expressing attenuated strain of Listeria (ΔactA, Lm) to explore immune responses in tumor-bearing mice after different injection methods [5]. - Intratumoral injection (i.t.) of Lm alone recruits neutrophils that convert to an immunosuppressive phenotype, creating an immune escape microenvironment that promotes tumor growth [6]. - Conversely, intravenous injection (i.v.) induces the production of anti-Lm cytotoxic CD8+ T cells, which infiltrate the tumor upon subsequent intratumoral injection, leading to tumor suppression through apoptosis induction and enhanced antigen presentation [7][8]. Group 2: Implications of Injection Timing - The study emphasizes the significance of injection timing, suggesting that prior intravenous injection activates systemic T cells, establishing an immune foundation for subsequent intratumoral injection, thus avoiding the immunosuppressive effects associated with intratumoral injection alone [10].

Core Viewpoint - The study highlights that intravesical administration of Bacillus Calmette-Guérin (BCG) vaccine can reprogram hematopoietic stem/progenitor cells (HSPC) to enhance anti-tumor immunity, indicating its potential in cancer immunotherapy [1][2][4][6]. Group 1: Mechanism of Action - BCG vaccine can colonize the bone marrow and reprogram HSPC, enhancing myeloid hematopoiesis in both mice and humans [3][4]. - The reprogrammed HSPC can generate neutrophils, monocytes, and dendritic cells, which reshape the tumor microenvironment and drive T cell-dependent anti-tumor responses [3][4]. Group 2: Key Findings - The study confirms that intravesical BCG administration leads to systemic reprogramming of HSPC [4]. - The reprogramming of HSPC is dependent on INFγ and enhances the antigen-presenting function of myeloid cells [4]. - Reprogrammed myeloid cells increase T cell infiltration and work synergistically with PD-1 blockade for anti-cancer effects [4][6]. Group 3: Implications - The findings underscore the broad potential of HSPC reprogramming in enhancing T cell-dependent tumor immunity, suggesting a novel approach in cancer treatment [6].