获得性耐药(acquired resistance),是指曾经用PD-1抑制剂起效过但是时间长了以后,肿瘤开始复发或者进展。 1 回顾性小样本研究:PD1耐药后直接切换PDL1,疗效有限,仍需更多证据支持 目前国内已经上市8种PD-1/PD-L1单抗,使用其中一款PD-1耐药后,能否切换为其他PD-1/PD-L1单抗,成为患者最直接最简单的想法。 一项日本...
[3]. Zaretsky J M,Garcia-Diaz A, Shin D S, et al. Mutations associated with acquired resistanceto PD-1 blockade in melanoma[J]. New England Journal of Medicine, 2016, 375(9):819-829.[4]. Saleh R, ElkordE. Acquired resistance to cancer immunotherapy: Role of tumor-mediatedimmunosuppre...
PD-1/PD-L1抑制剂临床的广泛使用,随之产生PD-1获得性耐药问题(Acquired Resistance),成为后PD-1时代的重要课题。无论是头颈部鳞癌和消化道肿瘤,这些对PD-1响应率低的肿瘤,还是霍奇金淋巴瘤和黑色素瘤等对PD-…
7、Zou, R., Wang, Y., Ye, F. et al. Mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade and the emerging role of gut microbiome. Clin Transl Oncol23, 2237–2252 (2021). https://doi.org/10.1007/s12094-021-02637-2 8、Fillon M. Fecal microbiota transplants may ...
上述7个步骤中任何一步出现问题,特别是T细胞招募、激活,都会影响PD-1/PD-L1抑制剂的临床获益,即出现免疫耐药。 免疫耐药主要分为:靶点缺失型耐药(Target-missingresistance,不表达PD-L1,或表达PD-L1但没有T淋巴细胞)、原发性耐药(肿瘤微环境中有PD-L1、T细胞,但对PD-1/PD-L1抑制剂无反应)、继发性耐药(肿瘤...
PD-1抗体作为一种免疫检验点抑制剂 (Immune checkpoint inhibitors) 已被FDA批准应用于多种肿瘤的临床治疗。但其在应用过程中面临着一个迫在眉睫的临床问题—获得性抗性 (Acquired Resistance) 问题,即部分肿瘤病人初始会对PD-1抗体的治疗产生应答,肿瘤缩小,但随后不久会呈现出对PD-1抗体治疗的抗性,肿瘤病情进一步进...
2021年11月1日,来自美国维克森林大学医学院的鲁勇课题组(现已任职于Houston Methodist/Weill Cornell Medicine,详情请见本文最后)在Nature Biomedical Engineering上发表了题为Elimination of acquired resistance to PD-1 blockade via the concurrent depletion of tumour cells and immunosuppressive cells的研究论文,首次...
参考文献: [1]. Schoenfeld A J, Rizvi H A, Memon D, et al. Systemic and oligo-acquired resistance to PD-(L) 1 blockade in lung cancer[J]. Clinical Cancer Research, 2022.
Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. N Engl J Med. 2016 Jul 13 Pitt JM, Vétizou M, Daillère R, Roberti MP, Yamazaki T, et al.Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intr...
More recently, mutations in JAK1 and JAK2, key factors of the signaling pathway JAKs/STATs, have been implicated in anti-PD-1 resistance. These mutations result in lack of response to interferon (IFN)-gamma and insensitivity to its antiproliferative effects. However, interferons also lead to ...