Vion Roman, Roulleaux-Dugage Matthieu, Flippot Ronan, Ouali Kaïssa, Rouanne Mathieu, Clatot Florian, Sellars MacLean, Champiat Stéphane, Chaput Nathalie, Massard Christophe, Danlos Francois-Xavier
Department of Medical Oncology, Henri Becquerel Institute, Rouen University, Rouen, France; INSERM U1245, IRON, Université de Rouen, Rouen, France.
Drug Development Department, Gustave Roussy, Université Paris Saclay, Villejuif, France; Immunomonitoring laboratory, L.I.O, CNRS 3655 and INSERM US 23 AMMICA, Gustave Roussy, Université Paris Saclay, Villejuif, France.
Eur J Cancer. 2025 Jul 25;225:115572. doi: 10.1016/j.ejca.2025.115572. Epub 2025 Jun 9.
Immune checkpoint blockade (ICB) have revolutionized medical oncology, with the occurrence of cures in situations regarded as palliative. However, most patients develop resistance and the selection of responders remains difficult. The search for predictive biomarkers for immunotherapy has revealed that tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) may be indicative of treatment effectiveness, since they may reflect the presence of an immune infiltrate with an anti-tumor effect. A better understanding of TLS neogenesis would help to establish anti-tumor strategies. For this purpose, this review outlines therapeutic modalities that could increase the immunogenicity and antigenicity of tumor cells, in particular immunogenic cell death (ICD), to turn "cold" tumors in "hot" tumors through interventions that promote the development of TLS. Second, the review describes the therapeutic strategies to enhance immune response against tumors, especially the resources to induce TLS, to strengthen cytotoxic T response / decrease Tregs and to promote the homing of immune cells. Future strategies should focus on a synergistic tactic combining both the enhancement of cancer cell immunogenicity and the stimulation of the immune system. PROVENANCE AND PEER REVIEW: Review commissioned by Aurelien Marabelle; externally peer reviewed.
免疫检查点阻断（ICB）彻底改变了医学肿瘤学，在原本被视为姑息治疗的情况下出现了治愈案例。然而，大多数患者会产生耐药性，且难以选择出有反应的患者。对免疫治疗预测生物标志物的研究表明，肿瘤微环境（TME）中的三级淋巴结构（TLS）可能预示着治疗效果，因为它们可能反映出具有抗肿瘤作用的免疫浸润的存在。更好地理解TLS的新生将有助于制定抗肿瘤策略。为此，本综述概述了可增强肿瘤细胞免疫原性和抗原性的治疗方式，特别是免疫原性细胞死亡（ICD），通过促进TLS发育的干预措施将“冷”肿瘤转变为“热”肿瘤。其次，综述描述了增强抗肿瘤免疫反应的治疗策略，尤其是诱导TLS的方法、增强细胞毒性T细胞反应/减少调节性T细胞以及促进免疫细胞归巢的资源。未来的策略应侧重于将增强癌细胞免疫原性和刺激免疫系统相结合的协同策略。来源和同行评审：由奥雷利安·马勒贝尔委托撰写的综述；外部同行评审。
