免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Targeting Peptidergic Systems for Melanoma Treatment.
Targeting Peptidergic Systems for Melanoma Treatment.
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黑色素瘤是一种异质性、复杂且侵袭性强的疾病,尽管近年来在分子靶向药物以及分子和遗传分析方面取得了进展,但它仍占皮肤癌死亡病例的约65%,而且不幸的是,在黑色素瘤III/IV期,生存率急剧下降。在年轻人中,黑色素瘤的发病率有所增加;因此,必须紧急研究新的治疗策略。肽能系统在抗击黑色素瘤的这些策略中发挥着关键作用。本综述的范围是展示单独靶向肽能系统,或与目前临床实践中用于治疗黑色素瘤的标准治疗策略联合治疗时所具有的巨大潜力。在这个意义上,将讨论一些关键点,如肽能系统与抗黑色素瘤治疗、致癌/抗黑色素瘤肽、肽受体、肽能系统、黑色素瘤风险与免疫系统的关系、临床相关性、肽能系统以及黑色素瘤中的递送策略。肽在黑色素瘤中发挥致癌、抗黑色素瘤以及致癌和抗黑色素瘤双重作用,在调控黑色素瘤发展方面表现出高度的功能复杂性。
大量抗黑色素瘤策略已被开发或重新定位用于潜在的临床应用,包括肽/肽受体抗体、肽受体拮抗剂或激动剂、酶抑制剂、CAR-巨噬细胞、microRNA和疫苗。肽递送以及防止酶降解的策略也已被开发出来。一些先前的抗黑色素瘤策略是基于黑色素瘤细胞中肽受体的表达/过表达,这对于诊断、黑色素瘤风险和进展及转移发展,以及对于应用更特异和更安全的抗黑色素瘤策略至关重要。对肽能系统进行细致而深入的研究可能有助于理解肽能系统如何调控黑色素瘤进展,并为可能应用于临床实践的治疗应用提供线索。本综述展示了单独靶向肽能系统或与目前临床实践中用于治疗黑色素瘤的标准治疗策略联合治疗的巨大潜力。从这些研究中获得的益处将是巨大的,因为基于迄今为止已开发的众多抗黑色素瘤策略,肽能系统是黑色素瘤中有前景的抗肿瘤靶点。
Melanoma is a heterogeneous, complex and aggressive disease that, despite recent advances in molecular-targeted drugs and molecular and genetic analysis, represents approximately 65% of skin cancer deaths, and unfortunately survival dramatically decreases in melanoma stages III/IV. In young people there is an increased incidence of developing melanoma; hence new therapeutic strategies must be urgently investigated. Peptidergic systems play a crucial role in these strategies to fight melanoma. The scope of this review is to show the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. In this sense, key points such as peptidergic systems and anti-melanoma treatments, oncogenic/anti-melanoma peptides, peptide receptors, peptidergic systems, melanoma risk and immune system relationships, clinical relevance, peptidergic systems and delivery strategies in melanoma will be discussed. Peptides exert oncogenic, anti-melanoma and dual oncogenic and anti-melanoma effects in melanoma, showing a high functional complexity in regulating melanoma development.
A plethora of anti-melanoma strategies have been developed or repurposed for potential clinical applications, including peptide/peptide receptor antibodies, peptide receptor antagonists or agonists, enzyme inhibitors, CAR-macrophages, microRNAs and vaccines. Strategies for peptide delivery and protection from enzymatic degradation have also been developed. Some of the previous anti-melanoma strategies are based on the expression/overexpression of peptide receptors in melanoma cells which is crucial for diagnosis, melanoma risk and progression and metastasis development and for the application of more specific and safer anti-melanoma strategies.
A meticulous and in-depth study of the peptidergic systems may help to understand how peptidergic systems regulate melanoma progression and shed light on possible therapeutic applications that can be applied in clinical practice.
This review shows the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. The benefits to be gained from these studies will be enormous because the peptidergic systems are promising antitumor targets in melanoma, based on the numerous anti-melanoma strategies that have been developed until now.
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