近日，南开大学免疫研究所的 曹雪涛 院士团队在《Cancer Cell》（IF 48.8）杂志上发表了题为 “Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1 （抑制癌症细胞内CD28通过靶向PD-L1增强抗肿瘤免疫并克服抗PD-1耐药性 ...

2019年12月17日 · Combined immunotherapy targeting the immune checkpoint receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1), or CTLA-4 and the PD-1 ligand (PD-L1) exhibits superior anti-tumor responses compared with single-agent therapy. Here, we examined the molecular b …

2017年3月9日 · Recent studies have demonstrated that the ability of anti–PD-L1/PD-1 therapy to restore antiviral (lymphocytic choriomeningitis virus, LCMV) and antitumor T cell responses depends on CD28 expression by T cells .

2025年3月4日 · We confirmed that NI-3201 blocks the PD-L1/PD-1 immune checkpoint pathway and conditionally provides T-cell co-stimulation via CD28 (signal 2) when engaging PD-L1+ tumors or immune cells.

2023年7月4日 · Upon stimulation with a CD3 antibody and recombinant PD-L1, all PD-1-CD28 IFP-transduced T cells triggered a measurable IFN-γ secretion, confirming their functionality and synergistic action...

2017年3月31日 · These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy.

PD-1 的全称是程序性死亡受体-1，属于CD28超家族成员，是由268个氨基酸组成的I型跨膜蛋白。 它是在1992年由日本京都大学的 Tasuku Honjo 教授发现的，可在T细胞、B细胞等免疫细胞表面表达。 不过在T细胞未活化时，几乎不表达PD-1，仅在T细胞活化之后，PD-1才在T细胞表面表达。 PD-L1 首次被发现是由华裔学者 陈列平 教授在1999年作为B7家族的第3个成员B7-H1。 次年，Tasuku Honjo与哈佛医学院的Gordon Freeman证实B7-H1能够与PD-1结合，抑制T细胞增殖 …

2025年1月13日 · To investigate how CD28 regulated PD-L1 expression in cancer cells, we performed CD28 immunoprecipitation following quantitative mass spectrometry analysis to identify potential CD28 protein interactome in 4T1 cells in response to IFNγ.

那接下来，该揭示cd28导致免疫逃逸的具体机制了：借助 单细胞rna测序 ，研究者们发现敲除cd28直接导致了tnbc细胞的pd-l1表达下调； 免疫共沉淀 实验则显示，cd28主要会与多种rna结合蛋白（rbps）发生相互作用，可能借助rbps影响pd-l1编码基因cd274 mrna的稳定性，但 ...

2025年3月1日 · CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion.