Hématologie-Immunothérapie, Institut du Cancer Avignon-Provence, Sainte Catherine, Avignon, France.
Faculté de médecine Montpellier, Université de Montpellier, Montpellier, France.
Front Immunol. 2021 Feb 23;12:595722. doi: 10.3389/fimmu.2021.595722. eCollection 2021.
Normal or "good" inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are produced to amplify the local inflammatory process followed by the migration of immune cells to the regional lymph nodes where adaptive immune response is initiated. Systemic inflammation enhances the biological response to mobilize additional cells from central and peripheral immune/hematopoietic system. Local mechanisms to limit inflammation are initiated and lead to healing. During the normal inflammatory process, there is a balance between the production of inflammatory chemokines/cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6 and IL-1 and the production of compounds that limit inflammation and have an immune suppressive effect, such as IL-10 and Transforming Factor (TGF) β. IL-6 and IL-6/soluble IL-6 Receptor (R) complex stimulate liver cells to produce inflammatory proteins, which represents the systemic inflammation response. The magnitude and the duration of the systemic inflammatory response are linked to the cause, under genetic and epigenetic control. Significant inflammation as seen in septic shock, in severe forms of infections or in certain active cancers, represents the "bad inflammation", correlated with a poor prognosis. In addition, the persistence of a chronic smoldering inflammation may lead to pathological situations which are observed in the majority of inflammatory, degenerative, dysmetabolic, or dysimmune diseases and cancer. Chronic smoldering inflammation is a cross between different pathological situations possibly linked. In addition, within the tumor microenvironment, inflammatory process results from different cellular mechanisms modulated by metabolic and vascular changes. On the contrary, a limited and balanced inflammation initiates the normal immune response, including the adaptive response which amplifies any immunotherapy, including vaccines. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells are associated with cytokine release syndrome, a clinical risk leading to the use of anti-cytokine drugs. Nowadays, it is time to monitor the dynamic inflammatory process for a better immune precision medicine in both infections and cancer.
正常或“有益”的炎症过程始于针对损伤或任何感染因子的局部细胞反应，伴随着中性粒细胞、巨噬细胞、朗格汉斯细胞、树突状细胞和固有免疫细胞的激活。细胞因子和趋化因子被产生以放大局部炎症过程，随后免疫细胞迁移到区域淋巴结，在那里启动适应性免疫反应。全身炎症增强了生物反应，从中央和外周免疫/造血系统动员更多的细胞。启动局部限制炎症的机制，导致愈合。在正常的炎症过程中，炎症趋化因子/细胞因子（如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-1）和限制炎症并有免疫抑制作用的化合物（如 IL-10 和转化因子（TGF）β）的产生之间存在平衡。IL-6 和 IL-6/可溶性 IL-6 受体（R）复合物刺激肝细胞产生炎症蛋白，代表全身炎症反应。全身炎症反应的幅度和持续时间与遗传和表观遗传控制下的原因有关。在败血症休克、严重感染或某些活动性癌症中观察到的显著炎症代表了“有害炎症”，与预后不良相关。此外，慢性潜伏性炎症的持续存在可能导致观察到的大多数炎症、退行性、代谢紊乱或免疫失调疾病和癌症中的病理情况。慢性潜伏性炎症是不同病理情况之间的交叉，可能存在联系。此外，在肿瘤微环境中，炎症过程是由代谢和血管变化调节的不同细胞机制引起的。相反，有限和平衡的炎症会引发正常的免疫反应，包括适应性反应，从而增强任何免疫疗法，包括疫苗。免疫检查点抑制剂和嵌合抗原受体（CAR）T 细胞与细胞因子释放综合征相关，这是一种导致使用抗细胞因子药物的临床风险。如今，是时候监测动态炎症过程，以便在感染和癌症中更好地进行免疫精准医学了。
