University of Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, LabEx LipSTIC, Besançon, France.
MED'INN'Pharma, Besançon, France.
Front Immunol. 2022 Jan 18;12:812171. doi: 10.3389/fimmu.2021.812171. eCollection 2021.
Cancers are consequences of cellular dysfunction leading to an aberrant cellular multiplication and proliferation, subsequently yielding metastasis formation. Inflammatory reaction, with immune cell recruitment, is the main defense against precancerous lesions. However, an inflammatory environment also favors cancer cell progression, with cancer cell evasion from immune surveillance, leading to cancer development. Current therapeutic strategies enhance this natural immune response in order to restore immunosurveillance. The variety of these strategies is a predominant source of inflammatory mediators used by cancer cells to grow, differentiate, and migrate, therefore encouraging metastasis formation. For this reason, during cancer progression, limiting inflammation appears to be an innovative strategy to avoid the escape of cancer cells and potentially enhance the efficacy of antitumor therapies. Thus, this study aims to investigate the impact of administering pro-resolving factors (SuperMApo drug candidate), which are inducers of inflammation resolution, in the framework of cancer treatment. We have observed that administering pro-resolving mediators issued from apoptotic cell efferocytosis by macrophages controlled peritoneal cancer progression by limiting cancer cell dissemination to the blood and mesenteric lymph nodes. This observation has been linked to an increase of macrophage mobilization in both peritoneal cavity and mesenteric lymph nodes. This control is associated to a restricted immunosuppressive myeloid cell circulation and to an IFN-γ-specific anti-tumor T-cell response. Altogether, these results suggest that administering proresolving factors could provide a new additional therapeutic alternative to control cancer progression.
癌症是细胞功能障碍导致异常细胞增殖和分裂的结果，随后导致转移形成。炎症反应伴随着免疫细胞的募集，是对抗癌前病变的主要防御机制。然而，炎症环境也有利于癌细胞的进展，癌细胞逃避免疫监视，导致癌症的发生。目前的治疗策略增强了这种天然免疫反应，以恢复免疫监视。这些策略的多样性是癌细胞用来生长、分化和迁移的炎症介质的主要来源，因此鼓励转移的形成。出于这个原因，在癌症进展过程中，限制炎症似乎是一种避免癌细胞逃逸并可能增强抗肿瘤治疗效果的创新策略。因此，本研究旨在研究在癌症治疗框架内给予促解决因子（SuperMApo 药物候选物）对炎症反应的影响。我们观察到，通过巨噬细胞吞噬凋亡细胞来诱导炎症消退，给予促解决介质可以控制腹膜癌细胞的进展，限制癌细胞向血液和肠系膜淋巴结的扩散。这一观察结果与巨噬细胞在腹腔和肠系膜淋巴结中的动员增加有关。这种控制与受限制的免疫抑制性髓样细胞循环和 IFN-γ 特异性抗肿瘤 T 细胞反应有关。总之，这些结果表明，给予促解决因子可能为控制癌症进展提供一种新的额外治疗选择。
