肿瘤细胞治疗研究
英文原题：B Cells and Tumor Immunometabolism: Emerging Insights into Immune Regulation and Therapeutic Resistance.
癌症进展和治疗耐药性是由恶性细胞与代谢改变的肿瘤微环境（TME）之间相互动态作用所塑造的。
癌症进展和治疗耐药性由恶性细胞与代谢改变的肿瘤微环境（TME）之间相互的动态相互作用所塑造。肿瘤相关缺氧、葡萄糖和氨基酸竞争、细胞外酸性、乳酸积累、腺苷、前列腺素E2（PGE2）及其他代谢信号可重塑免疫细胞功能，并决定炎症是杀肿瘤的还是支持肿瘤的。尽管B淋巴细胞传统上被视为产生抗体的细胞，但肿瘤浸润B（TIL-B）细胞包含功能异质的群体，可作为抗原呈递细胞、细胞因子和趋化因子产生者、抗体分泌细胞、细胞毒性效应细胞、调节性B细胞（Bregs）以及三级淋巴结构（TLSs）的组织者。它们的功能状态受到其所处代谢和空间环境的强烈影响。本综述聚焦于B细胞生物学与肿瘤免疫代谢的交叉领域，强调缺氧、乳酸、营养限制、腺苷、PGE2、犬尿氨酸和B细胞来源的γ-氨基丁酸（GABA）如何塑造B细胞状态及其与髓系和淋巴系细胞的相互作用。我们讨论代谢条件下形成的Bregs和免疫球蛋白（Ig）A偏斜的体液反应如何促进免疫抑制，而代谢能力强的抗原呈递、IgG偏斜和TLS相关的B细胞反应可能支持有效的抗肿瘤免疫。重要的是，这些效应具有肿瘤类型和情境依赖性：B细胞/TLS特征与多种乳腺癌、肺癌及其他实体瘤的良好预后相关，而以B细胞为中心的免疫景观在胰腺癌中可能被抑制或呈中性，以IgA为主的反应在特定恶性肿瘤中可能不利。我们进一步探讨这些状态如何影响对免疫检查点阻断、化疗、放疗和细胞治疗的敏感性或耐药性。最后，我们强调B细胞代谢通路作为潜在治疗切入点，并指出空间代谢组学和前瞻性干预研究的优先方向。
Cancer progression and therapeutic resistance are shaped by reciprocal dynamic interactions between malignant cells and the metabolically altered tumor microenvironment (TME). Tumor-associated hypoxia, glucose and amino acid competition, extracellular acidity, lactate accumulation, adenosine, prostaglandin E2 (PGE2) and other metabolic signals can remodel immune cell function and determine whether inflammation is tumoricidal or tumor-supportive. Although B lymphocytes have traditionally been viewed as antibody-producing cells, tumor-infiltrating B (TIL-B) cells comprise functionally heterogeneous populations that can act as antigen-presenting cells, cytokine and chemokine producers, antibody-secreting cells, cytotoxic effectors, regulatory B cells (Bregs) and organizers of tertiary lymphoid structures (TLSs). Their functional state is strongly influenced by the metabolic and spatial context in which they reside. This review focuses on the intersection of B cell biology and tumor immunometabolism, emphasizing how hypoxia, lactate, nutrient limitation, adenosine, PGE2, kynurenine and B cell-derived γ-aminobutyric acid (GABA) may shape B cell states and their interactions with myeloid and lymphoid cells. We discuss how metabolically conditioned Bregs and immunoglobulin (Ig)A-skewed humoral responses can contribute to immune suppression, whereas metabolically competent antigen-presenting, IgG-biased and TLS-associated B cell responses may support effective anti-tumor immunity. Importantly, the effects are tumor type- and context-dependent: B cell/TLS signatures are associated with favorable outcomes in several breast, lung and other solid tumors, whereas B cell-centered immune landscapes can be suppressed or neutral in pancreatic cancer and IgA-dominated responses may be unfavorable in selected malignancies. We further examine how these states may influence sensitivity or resistance to immune checkpoint blockade, chemotherapy, radiotherapy and cellular therapies. Finally, we highlight B cell metabolic pathways as potential therapeutic entry points and identify priorities for spatial metabolomics and prospective interventional studies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
