2.Liu SY1, Wu YL, Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China. J Hematol Oncol. 2017 Jul 5;10(1):136. d 3.Zhang Q, Liao Y, Chen J, Cai B, Su Z, Ying B, et al. Epidemiology stud...
et al. Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors[J]. Front Cell Dev Biol...
Epigenetically silenced PD-L1 confers drug resistance to anti-PD1 therapy in gastric cardia adenocarcinomaPD-Ll promoter methylationGastric cardia adenocarcinomaAnti-PD-1 therapyGCAThe anti-PD-1/PD-L1 therapy has been demonstrated safe and effective for cancer patients. However, our previous data ...
当黑色素瘤患者无法响应PD-1阻断疗法时,并不是所有人都是出于同样的原因。通过将免疫响应的复苏与肿瘤负担进行关联,这项研究强调了检查点抑制剂治疗可能失败的3种途径:1)药物并没有引发复苏(re-invigorated)的免疫响应;2)产生的免疫反应不足以应对肿瘤的大小;3)药效是脱靶的(the drug effect is off target)。
However, PD-1/PD-L1 could also prevent the activation of T cells in the tumor and thus result in immune resistance [5]. PD-1/PD-L1 blockade is a breakthrough in cancer immunotherapy, and it has been trialed in a broad range of malignancies in the preclinical or clinical stage, ...
PD-1/PD-L1抑制剂获批适应症 截止至2020年3月,FDA批准了多个免疫检查点抑制剂在多瘤肿中的适应症。 [Immune-checkpoint inhibitor approval status by the Food and Drug Administration (access date: 03/13/2020). A: accelerated, AB: antibody, CTx: chemotherapy, dMMR: mismatch repair deficiency, HCC:...
PD-1-Fc bead-treated myeloma cells also became resistant to apoptosis that was induced by melphalan and the proteasome inhibitor bortezomib. Apoptosis resistance was associated with the PI3K/AKT pathway. Both myeloma cell drug resistance and antiapoptotic responses occurred through the PI3K/AKT ...
but so far, the successful use of PD-1/PD-L1 inhibitors has been hindered by low efficiency and consistent drug-resistance [2]. Degradation technologies for proteins of interest (POIs), such as the proteolysis-targeting chimera (PROTAC) system, have huge potential for overcoming these problems...
Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic and RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated collagen correlates with decreased total CD8+T cells and increased exhaust...
[1] Boussiotis VA, Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med. 2016;375:1767-78 [2] Mahoney KM, Rennert PD, Freeman GL, Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov.2015;14:561-84 ...