The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors.
The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors.
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DOI：
10.3390/cancers12102983
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发表时间：
2020-10-15
期刊：
影响因子：
5.2
通讯作者：
Watabe K
中科院分区：
文献类型：
--
作者：
Deshpande RP;Sharma S;Watabe K
人体免疫系统具有强大的能力，可以控制体内非自然细胞的生长，以抑制癌症的进展。然而，负责预防癌症生长的免疫系统的细胞和分子在患有这种疾病的患者中往往受到严重损害。因此，为了引发针对癌症的功能性免疫反应，科学家们开发了被称为检查点抑制剂（CPI）的抗体，该抗体释放受损的免疫细胞并增强它们的癌症杀伤能力。尽管CPI彻底改变了某些癌症的治疗，但许多患者对CPI没有反应，并且治疗结果在癌症类型之间不成比例地变化。本文综述了生活方式，代谢和社会学因素如何发挥作用，在决定CPI治疗的结果。我们还讨论了通过减轻这些混杂变量的影响来提高CPI功效的潜在方法。检查点阻断免疫疗法（CPI）是许多类型癌症的有效治疗选择。无论其广泛的临床意义，总体疗效仍然是不可预测的，甚至在某些病理，如乳腺癌差。因此，必须了解影响其反应能力的因素的作用。在这篇综述中，我们提供了一个概述参与社会学因素，生活方式和代谢紊乱在调节CPI反应的患者从多种恶性肿瘤。包括运动和饮食在内的生活方式习惯促进了治疗反应性，而饮酒通过减少突变负担和阻碍树突状细胞的抗原呈递来减轻CPI效应。代谢紊乱如肥胖被认为会增强PD-1的表达，而糖尿病和高血压是CPI治疗的结果而不是原因。在社会学因素中，性别和种族对CPI有效性产生积极影响，因为效应T细胞活性增加，PD-1表达增加，而衰老通过减少功能性T细胞和增加毒性损害CPI反应性。这些因素的综合影响，观察肥胖和性别，其中肥胖男性的CPI的影响最显着。因此，在治疗CPI患者之前应仔细考虑这些变量，以获得最佳治疗结果。
The human immune system is robustly equipped to keep unnatural cell growth in check in the body to suppress cancer progression. However, the cells and molecules of the immune system responsible for preventing cancer growth are often severely compromised in patients harboring this disease. Therefore, to elicit a functional immune response against cancer, scientists have developed antibodies, known as checkpoint inhibitors (CPI), which unleash the compromised immune cells and potentiate them with cancer killing ability. Although CPI revolutionized the treatment of certain cancers, many patients do not respond to the CPI and the treatment outcome varies disproportionately between cancer types. This review elaborates on how lifestyle, metabolic and sociological factors play a role in determining the outcome of CPI treatment. We also discuss potential ways to enhance CPI efficacy by mitigating the effect of these confounding variables. Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.
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PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
16.6
作者：
Burton, Bronwen R.;Britton, Graham J.;Fang, Hai;Verhagen, Johan;Smithers, Ben;Sabatos-Peyton, Catherine A.;Carney, Laura J.;Gough, Julian;Strobel, Stephan;Wraith, David C.
通讯作者：
Wraith, David C.
DOI：
10.1152/ajpgi.2001.280.6.g1280
发表时间：
2001-06-01
影响因子：
4.5
作者：
Atkinson, KJ;Rao, RK
通讯作者：
Rao, RK
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators