Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers.
Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers.
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DOI：
10.1186/s40425-018-0376-0
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发表时间：
2018-07-03
影响因子：
10.9
通讯作者：
Asimakopoulos F
中科院分区：
文献类型：
--
作者：
Mushtaq MU;Papadas A;Pagenkopf A;Flietner E;Morrow Z;Chaudhary SG;Asimakopoulos F
我们对细胞串扰动力学的最新了解进展突出了宿主抗肿瘤效应的重要性，这种效应可以通过免疫疗法来利用。肿瘤利用免疫检查点来逃避适应性免疫反应。在过去的十年里，随着免疫检查点抑制物(ICIS)、抗细胞毒性T淋巴细胞抗原4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)或它们的配体，如PD1配体1(PD-L1)的发展，肿瘤免疫治疗经历了一场革命。据报道，ICIS具有广泛的抗肿瘤活性，在实体器官和血液系统的恶性肿瘤环境中都是如此。然而，只有不到三分之一的患者实现了持久和有意义的治疗反应。免疫检查点配体(如PD-L1)的表达、突变负荷和肿瘤浸润性淋巴细胞目前被用作预测ICIS反应的生物标志物。然而，他们并不能可靠地预测哪些患者将从这些疗法中受益。迫切需要发现新的生物标记物来预测治疗效果，并确定开发组合策略以提高应答率的领域。新的证据表明，肿瘤细胞外基质(ECM)成分及其蛋白水解性重塑产物在调节癌症免疫循环的每一步中发挥着关键作用。在此，我们综述了抗肿瘤免疫反应和免疫治疗背景下的肿瘤基质动力学和基质重塑，并建议探索基于基质的生物标记物来确定免疫治疗的候选者。
Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy.
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影响因子：
4.4
作者：
Bose, Anamika;Barik, Subhasis;Majumdar, Subrata
通讯作者：
Majumdar, Subrata
影响因子：
6.8
作者：
Cathcart, Jillian;Pulkoski-Gross, Ashleigh;Cao, Jian
通讯作者：
Cao, Jian
影响因子：
15.9
作者：
Abramsson, A;Lindblom, P;Betsholtz, C
通讯作者：
Betsholtz, C
影响因子：
3.9
作者：
Adotevi, Olivier;Pere, Helene;Tartour, Eric
通讯作者：
Tartour, Eric
DOI：
10.1056/nejmoa1504627
发表时间：
2015-07-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer J;Reckamp KL;Baas P;Crinò L;Eberhardt WE;Poddubskaya E;Antonia S;Pluzanski A;Vokes EE;Holgado E;Waterhouse D;Ready N;Gainor J;Arén Frontera O;Havel L;Steins M;Garassino MC;Aerts JG;Domine M;Paz-Ares L;Reck M;Baudelet C;Harbison CT;Lestini B;Spigel DR
通讯作者：
Spigel DR