Research progress of post-translational modifications of programmed death-1 in tumor immunotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Xu ¹ , XU Jianjiang ¹ , MA Mingli ¹ , CHEN Yan ¹ ,  JIANG Lei ²

1. The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding?author：

JIANG Lei, Email: jiangyjsggyx@163.com

Keywords：

programmed death-1; post-translation embellishment; tumor immunity; immunotherapy

DOI：

10.7507/1007-9424.202509099

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically summarize the application prospects of post-translational modifications of programmed death-1 (PD-1) in tumor immunotherapy, and provide new ideas for the immunotherapy of tumor patients. Methods Based on the immunosuppressive mechanism of PD-1 and the clinical application status of anti PD-1 immunotherapy, combined with the existing research results on PD-1 post-translational modifications, this study systematically sorted out and analyzed the types of post-translational modifications of PD-1, their regulatory mechanisms, and their association with immunotherapy. Results PD-1 is an immunosuppressive molecule expressed on the surface of activated T cells, B cells and other cells. After binding to programmed death-ligand 1, it can negatively regulate the immune system. Anti PD-1/programmed death-ligand 1 immunotherapy has been widely used in the treatment of various malignant tumors, but some patients have poor response. PD-1 has various post-translational modifications such as phosphorylation, glycosylation, ubiquitination and palmitoylation, which can affect the stability and physiological functions of PD-1. Conclusions Post-translational modifications of PD-1 are a key mechanism regulating the tumor immune evasion. Targeting the post-translational modification process of PD-1 is expected to improve the response of tumor immunotherapy and have good clinical application prospects.

Citation： WANG Xu, XU Jianjiang, MA Mingli, CHEN Yan, JIANG Lei. Research progress of post-translational modifications of programmed death-1 in tumor immunotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(5): 704-710. doi: 10.7507/1007-9424.202509099 Copy

1.	Martínez-Jiménez F, Chowell D. Genetic immune escape in cancer: timing and implications for treatment. Trends Cancer, 2025, 11(4): 286-294.
2.	Wang J, Chen Q, Shan Q, et al. Clinical development of immuno-oncology therapeutics. Cancer Lett, 2025, 617: 217616. doi: 10.1016/j.canlet.2025.217616.
3.	Kaviyarasan V, Das A, Deka D, et al. Advancements in immunotherapy for colorectal cancer treatment: a comprehensive review of strategies, challenges, and future prospective. Int J Colorectal Dis, 2024, 40(1): 1. doi: 10.1007/s00384-024-04790-w.
4.	Hsieh HC, Ling LL, Wang YC. Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications. J Biomed Sci, 2026, 33(1): 3. doi: 10.1186/s12929-025-01202-1.
5.	Chen L, Huang L, Gu Y, et al. Novel post-translational modifications of protein by metabolites with immune responses and immune-related molecules in cancer immunotherapy. Int J Biol Macromol, 2024, 277(Pt 1): 133883. doi: 10.1016/j.ijbiomac.2024.133883.
6.	Li Z, Yu X, Yuan Z, et al. New horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer. Biochim Biophys Acta Rev Cancer, 2024, 1879(5): 189152. doi: 10.1016/j.bbcan.2024.189152.
7.	Tang J, Liu H, Li J, et al. Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics. Future Med Chem, 2024, 16(15): 1583-1599.
8.	Yang Y, Zhang E, Mao X, et al. Targeting palmitoylation: a novel frontier in cancer biology and immunotherapy. Biochim Biophys Acta Rev Cancer, 2026, 1881(1): 189509. doi: 10.1016/j.bbcan.2025.189509.
9.	Hu Q, Shi Y, Wang H, et al. Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy. Exp Hematol Oncol, 2025, 14(1): 37. doi: 10.1186/s40164-025-00627-6.
10.	Wang SL, Chan TA. Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy. Cancer Cell, 2025, 43(4): 641-664.
11.	Lu J, Yu D, Li H, et al. Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy. Phytother Res, 2025, 39(4): 1735-1757.
12.	Zhao Y, Jiang L. Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance. Trends Cell Biol, 2025, 35(8): 667-677.
13.	Asmamaw MD, Shi XJ, Zhang LR, et al. A comprehensive review of SHP2 and its role in cancer. Cell Oncol (Dordr), 2022, 45(5): 729-753.
14.	Arneth B. Molecular mechanisms of immune regulation: a review. Cells, 2025, 14(4): 283. doi: 10.3390/cells14040283.
15.	Bardhan K, Aksoylar HI, Le Bourgeois T, et al. Publisher correction: phosphorylation of PD-1-Y248 is a marker of PD-1-mediated inhibitory function in human T cells. Sci Rep, 2020, 10(1): 15905. doi: 10.1038/s41598-020-71090-y.
16.	Xiao X, Shi J, He C, et al. ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy. Nat Commun, 2023, 14(1): 2859. doi: 10.1038/s41467-023-38605-3.
17.	Yang D, Yang C, Huang L, et al. Role of ubiquitination-driven metabolisms in oncogenesis and cancer therapy. Semin Cancer Biol, 2025, 110: 17-35.
18.	Zhou X, Fu C, Chen X. The role of ubiquitin pathway-mediated regulation of immune checkpoints in cancer immunotherapy. Cancer, 2023, 129(11): 1649-1661.
19.	Wu Y, Lin Y, Shen F, et al. FBXO38 deficiency promotes lysosome-dependent STING degradation and inhibits cGAS-STING pathway activation. Neoplasia, 2024, 49: 100973. doi: 10.1016/j.neo.2024.100973.
20.	Dibus N, Salyova E, Kolarova K, et al. FBXO38 is dispensable for PD-1 regulation. EMBO Rep, 2024, 25(10): 4206-4225.
21.	Meng X, Liu X, Guo X, et al. FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells. Nature, 2018, 564(7734): 130-135.
22.	Zhou XA, Zhou J, Zhao L, et al. KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression. Proc Natl Acad Sci U S A, 2020, 117(45): 28239-28250.
23.	Wang W, Liu X, Zhao L, et al. FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects. Front Pharmacol, 2024, 15: 1505027. doi: 10.3389/fphar.2024.1505027.
24.	Zhong L, Zhang Y, Li M, et al. E3 ligase FBXW7 restricts M2-like tumor-associated macrophage polarization by targeting c-Myc. Aging (Albany NY), 2020, 12(23): 24394-24423.
25.	He J, Song Y, Li G, et al. Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation. J Clin Invest, 2019, 129(9): 3877-3893.
26.	Liu J, Wei L, Hu N, et al. FBW7-mediated ubiquitination and destruction of PD-1 protein primes sensitivity to anti-PD-1 immunotherapy in non-small cell lung cancer. J Immunother Cancer, 2022, 10(9): e005116. doi: 10.1136/jitc-2022-005116.
27.	Zeng Q, Zeng S, Dai X, et al. MDM2 inhibitors in cancer immunotherapy: current status and perspective. Genes Dis, 2024, 11(6): 101279. doi: 10.1016/j.gendis.2024.101279.
28.	Wu Z, Cao Z, Yao H, et al. Coupled deglycosylation-ubiquitination cascade in regulating PD-1 degradation by MDM2. Cell Rep, 2023, 42(7): 112693. doi: 10.1016/j.celrep.2023.112693.
29.	Langenbach M, Giesler S, Richtsfeld S, et al. MDM2 inhibition enhances immune checkpoint inhibitor efficacy by increasing IL15 and MHC class Ⅱ production. Mol Cancer Res, 2023, 21(8): 849-864.
30.	Lu D, Xu Z, Zhang D, et al. PD-1 N58-glycosylation-dependent binding of monoclonal antibody cemiplimab for immune checkpoint therapy. Front Immunol, 2022, 13: 826045. doi: 10.3389/fimmu.2022.826045.
31.	Duan Z, Shi R, Gao B, et al. N-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment. J Transl Med, 2024, 22(1): 705. doi: 10.1186/s12967-024-05502-2.
32.	Cao Y, Yi W, Zhu Q. Glycosylation in the tumor immune response: the bitter side of sweetness. Acta Biochim Biophys Sin (Shanghai), 2024, 56(8): 1184-1198.
33.	Sun L, Li CW, Chung EM, et al. Targeting glycosylated PD-1 induces potent antitumor immunity. Cancer Res, 2020, 80(11): 2298-2310.
34.	Chen Q, Tan Z, Tang Y, et al. Comprehensive glycomic and glycoproteomic analyses of human programmed cell death protein 1 extracellular domain. J Proteome Res, 2024, 23(9): 3958-3973.
35.	Pan Q, Zhang XL. Roles of core fucosylation modification in immune system and diseases. Cell Insight, 2024, 4(1): 100211. doi: 10.1016/j.cellin.2024.100211.
36.	Okada M, Chikuma S, Kondo T, et al. Blockage of core fucosylation reduces cell-surface expression of PD-1 and promotes anti-tumor immune responses of T cells. Cell Rep, 2017, 20(5): 1017-1028.
37.	Chu CW, ?aval T, Alisson-Silva F, et al. Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors. Life Sci Alliance, 2024, 7(3): e202302368. doi: 10.26508/lsa.202302368.
38.	Liu K, Tan S, Jin W, et al. N-glycosylation of PD-1 promotes binding of camrelizumab. EMBO Rep, 2020, 21(12): e51444. doi: 10.15252/embr.202051444.
39.	Wang M, Wang J, Wang R, et al. Identification of a monoclonal antibody that targets PD-1 in a manner requiring PD-1 Asn58 glycosylation. Commun Biol, 2019, 2: 392. doi: 10.1038/s42003-019-0642-9.
40.	Liao C, An J, Tan Z, et al. Changes in protein glycosylation in head and neck squamous cell carcinoma. J Cancer, 2021, 12(5): 1455-1466.
41.	Qian YR, Zhao YJ, Zhang F. Protein palmitoylation: biological functions, disease, and therapeutic targets. MedComm (2020), 2025, 6(3): e70096. doi: 10.1002/mco2.70096.
42.	Yao H, Li C, He F, et al. A peptidic inhibitor for PD-1 palmitoylation targets its expression and functions. RSC Chem Biol, 2020, 2(1): 192-205.
43.	Millrine D, Peter JJ, Kulathu Y. A guide to UFMylation, an emerging posttranslational modification. FEBS J, 2023, 290(21): 5040-5056.
44.	Zhou J, Ma X, He X, et al. Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target. Proc Natl Acad Sci U S A, 2023, 120(11): e2215732120. doi: 10.1073/pnas.2215732120.
45.	He C, Xing X, Chen HY, et al. UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity. Mol Cell, 2024, 84(6): 1120-1138.
46.	Chen F, Yu Y, Cai X, et al. Immune checkpoint inhibitors and immunomodulators for cancer immunotherapy: insights into resistance and therapeutic strategies. Adv Sci (Weinh), 2026: e21355. doi: 10.1002/advs.202521355.
47.	Dai X, Gao Y, Wei W. Post-translational regulations of PD-L1 and PD-1: mechanisms and opportunities for combined immunotherapy. Semin Cancer Biol, 2022, 85: 246-252.
48.	Gao M, Shi J, Xiao X, et al. PD-1 regulation in immune homeostasis and immunotherapy. Cancer Lett, 2024, 588: 216726. doi: 10.1016/j.canlet.2024.216726.
49.	LaMarche MJ, Acker M, Argintaru A, et al. Identification of TNO155, an allosteric SHP2 inhibitor for the treatment of cancer. J Med Chem, 2020, 63(22): 13578-13594.
50.	Chen X, Keller SJ, Hafner P, et al. Tyrosine phosphatase PTPN11/ SHP2 in solid tumors - bull’s eye for targeted therapy? Front Immunol, 2024, 15: 1340726. doi: 10.3389/fimmu.2024.1340726.
51.	Li CW, Lim SO, Chung EM, et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell, 2018, 33(2): 187-201.
52.	Zhang Q, Yang Z, Hao X, et al. Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling. Cell Biosci, 2023, 13(1): 192. doi: 10.1186/s13578-023-01137-w.
53.	Huang HC, Lai YJ, Liao CC, et al. Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. EBioMedicine, 2021, 74: 103712. doi: 10.1016/j.ebiom.2021.103712.
54.	Miao YR, Thakkar KN, Qian J, et al. Neutralization of PD-L2 is essential for overcoming immune checkpoint blockade resistance in ovarian cancer. Clin Cancer Res, 2021, 27(15): 4435-4448.
55.	Madhukar G, Haque MA, Khan S, et al. E3 ubiquitin ligases and their therapeutic potential in disease management. Biochem Pharmacol, 2025, 236: 116875. doi: 10.1016/j.bcp.2025.116875.
56.	Zhang H, Zhang Y, Feng Z, et al. Discovery of novel proteolysis-targeting chimera molecules as degraders of programmed cell death-ligand 1 for breast cancer therapy. J Med Chem, 2024, 67(13): 10589-10600.
57.	Dai MY, Shi YY, Wang AJ, et al. High-potency PD-1/PD-L1 degradation induced by Peptide-PROTAC in human cancer cells. Cell Death Dis, 2022, 13(11): 924. doi: 10.1038/s41419-022-05375-7.
58.	Sun C, Liu S, Lau JW, et al. Enzyme-activated orthogonal proteolysis chimeras for tumor microenvironment-responsive immunomodulation. Angew Chem Int Ed Engl, 2025, 64(22): e202423057. doi: 10.1002/anie.202423057.
59.	Diao H, Chen J, Zhang Y, et al. BRD4 orchestrates the metabolic-epigenetic regulation of GM-CSF expression and secretion to drive PD-L1+ macrophage-mediated immune evasion in triple-negative breast cancer. Oncogene, 2026, 45(9): 856-874.

1. Martínez-Jiménez F, Chowell D. Genetic immune escape in cancer: timing and implications for treatment. Trends Cancer, 2025, 11(4): 286-294.
2. Wang J, Chen Q, Shan Q, et al. Clinical development of immuno-oncology therapeutics. Cancer Lett, 2025, 617: 217616. doi: 10.1016/j.canlet.2025.217616.
3. Kaviyarasan V, Das A, Deka D, et al. Advancements in immunotherapy for colorectal cancer treatment: a comprehensive review of strategies, challenges, and future prospective. Int J Colorectal Dis, 2024, 40(1): 1. doi: 10.1007/s00384-024-04790-w.
4. Hsieh HC, Ling LL, Wang YC. Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications. J Biomed Sci, 2026, 33(1): 3. doi: 10.1186/s12929-025-01202-1.
5. Chen L, Huang L, Gu Y, et al. Novel post-translational modifications of protein by metabolites with immune responses and immune-related molecules in cancer immunotherapy. Int J Biol Macromol, 2024, 277(Pt 1): 133883. doi: 10.1016/j.ijbiomac.2024.133883.
6. Li Z, Yu X, Yuan Z, et al. New horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer. Biochim Biophys Acta Rev Cancer, 2024, 1879(5): 189152. doi: 10.1016/j.bbcan.2024.189152.
7. Tang J, Liu H, Li J, et al. Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics. Future Med Chem, 2024, 16(15): 1583-1599.
8. Yang Y, Zhang E, Mao X, et al. Targeting palmitoylation: a novel frontier in cancer biology and immunotherapy. Biochim Biophys Acta Rev Cancer, 2026, 1881(1): 189509. doi: 10.1016/j.bbcan.2025.189509.
9. Hu Q, Shi Y, Wang H, et al. Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy. Exp Hematol Oncol, 2025, 14(1): 37. doi: 10.1186/s40164-025-00627-6.
10. Wang SL, Chan TA. Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy. Cancer Cell, 2025, 43(4): 641-664.
11. Lu J, Yu D, Li H, et al. Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy. Phytother Res, 2025, 39(4): 1735-1757.
12. Zhao Y, Jiang L. Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance. Trends Cell Biol, 2025, 35(8): 667-677.
13. Asmamaw MD, Shi XJ, Zhang LR, et al. A comprehensive review of SHP2 and its role in cancer. Cell Oncol (Dordr), 2022, 45(5): 729-753.
14. Arneth B. Molecular mechanisms of immune regulation: a review. Cells, 2025, 14(4): 283. doi: 10.3390/cells14040283.
15. Bardhan K, Aksoylar HI, Le Bourgeois T, et al. Publisher correction: phosphorylation of PD-1-Y248 is a marker of PD-1-mediated inhibitory function in human T cells. Sci Rep, 2020, 10(1): 15905. doi: 10.1038/s41598-020-71090-y.
16. Xiao X, Shi J, He C, et al. ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy. Nat Commun, 2023, 14(1): 2859. doi: 10.1038/s41467-023-38605-3.
17. Yang D, Yang C, Huang L, et al. Role of ubiquitination-driven metabolisms in oncogenesis and cancer therapy. Semin Cancer Biol, 2025, 110: 17-35.
18. Zhou X, Fu C, Chen X. The role of ubiquitin pathway-mediated regulation of immune checkpoints in cancer immunotherapy. Cancer, 2023, 129(11): 1649-1661.
19. Wu Y, Lin Y, Shen F, et al. FBXO38 deficiency promotes lysosome-dependent STING degradation and inhibits cGAS-STING pathway activation. Neoplasia, 2024, 49: 100973. doi: 10.1016/j.neo.2024.100973.
20. Dibus N, Salyova E, Kolarova K, et al. FBXO38 is dispensable for PD-1 regulation. EMBO Rep, 2024, 25(10): 4206-4225.
21. Meng X, Liu X, Guo X, et al. FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells. Nature, 2018, 564(7734): 130-135.
22. Zhou XA, Zhou J, Zhao L, et al. KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression. Proc Natl Acad Sci U S A, 2020, 117(45): 28239-28250.
23. Wang W, Liu X, Zhao L, et al. FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects. Front Pharmacol, 2024, 15: 1505027. doi: 10.3389/fphar.2024.1505027.
24. Zhong L, Zhang Y, Li M, et al. E3 ligase FBXW7 restricts M2-like tumor-associated macrophage polarization by targeting c-Myc. Aging (Albany NY), 2020, 12(23): 24394-24423.
25. He J, Song Y, Li G, et al. Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation. J Clin Invest, 2019, 129(9): 3877-3893.
26. Liu J, Wei L, Hu N, et al. FBW7-mediated ubiquitination and destruction of PD-1 protein primes sensitivity to anti-PD-1 immunotherapy in non-small cell lung cancer. J Immunother Cancer, 2022, 10(9): e005116. doi: 10.1136/jitc-2022-005116.
27. Zeng Q, Zeng S, Dai X, et al. MDM2 inhibitors in cancer immunotherapy: current status and perspective. Genes Dis, 2024, 11(6): 101279. doi: 10.1016/j.gendis.2024.101279.
28. Wu Z, Cao Z, Yao H, et al. Coupled deglycosylation-ubiquitination cascade in regulating PD-1 degradation by MDM2. Cell Rep, 2023, 42(7): 112693. doi: 10.1016/j.celrep.2023.112693.
29. Langenbach M, Giesler S, Richtsfeld S, et al. MDM2 inhibition enhances immune checkpoint inhibitor efficacy by increasing IL15 and MHC class Ⅱ production. Mol Cancer Res, 2023, 21(8): 849-864.
30. Lu D, Xu Z, Zhang D, et al. PD-1 N58-glycosylation-dependent binding of monoclonal antibody cemiplimab for immune checkpoint therapy. Front Immunol, 2022, 13: 826045. doi: 10.3389/fimmu.2022.826045.
31. Duan Z, Shi R, Gao B, et al. N-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment. J Transl Med, 2024, 22(1): 705. doi: 10.1186/s12967-024-05502-2.
32. Cao Y, Yi W, Zhu Q. Glycosylation in the tumor immune response: the bitter side of sweetness. Acta Biochim Biophys Sin (Shanghai), 2024, 56(8): 1184-1198.
33. Sun L, Li CW, Chung EM, et al. Targeting glycosylated PD-1 induces potent antitumor immunity. Cancer Res, 2020, 80(11): 2298-2310.
34. Chen Q, Tan Z, Tang Y, et al. Comprehensive glycomic and glycoproteomic analyses of human programmed cell death protein 1 extracellular domain. J Proteome Res, 2024, 23(9): 3958-3973.
35. Pan Q, Zhang XL. Roles of core fucosylation modification in immune system and diseases. Cell Insight, 2024, 4(1): 100211. doi: 10.1016/j.cellin.2024.100211.
36. Okada M, Chikuma S, Kondo T, et al. Blockage of core fucosylation reduces cell-surface expression of PD-1 and promotes anti-tumor immune responses of T cells. Cell Rep, 2017, 20(5): 1017-1028.
37. Chu CW, ?aval T, Alisson-Silva F, et al. Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors. Life Sci Alliance, 2024, 7(3): e202302368. doi: 10.26508/lsa.202302368.
38. Liu K, Tan S, Jin W, et al. N-glycosylation of PD-1 promotes binding of camrelizumab. EMBO Rep, 2020, 21(12): e51444. doi: 10.15252/embr.202051444.
39. Wang M, Wang J, Wang R, et al. Identification of a monoclonal antibody that targets PD-1 in a manner requiring PD-1 Asn58 glycosylation. Commun Biol, 2019, 2: 392. doi: 10.1038/s42003-019-0642-9.
40. Liao C, An J, Tan Z, et al. Changes in protein glycosylation in head and neck squamous cell carcinoma. J Cancer, 2021, 12(5): 1455-1466.
41. Qian YR, Zhao YJ, Zhang F. Protein palmitoylation: biological functions, disease, and therapeutic targets. MedComm (2020), 2025, 6(3): e70096. doi: 10.1002/mco2.70096.
42. Yao H, Li C, He F, et al. A peptidic inhibitor for PD-1 palmitoylation targets its expression and functions. RSC Chem Biol, 2020, 2(1): 192-205.
43. Millrine D, Peter JJ, Kulathu Y. A guide to UFMylation, an emerging posttranslational modification. FEBS J, 2023, 290(21): 5040-5056.
44. Zhou J, Ma X, He X, et al. Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target. Proc Natl Acad Sci U S A, 2023, 120(11): e2215732120. doi: 10.1073/pnas.2215732120.
45. He C, Xing X, Chen HY, et al. UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity. Mol Cell, 2024, 84(6): 1120-1138.
46. Chen F, Yu Y, Cai X, et al. Immune checkpoint inhibitors and immunomodulators for cancer immunotherapy: insights into resistance and therapeutic strategies. Adv Sci (Weinh), 2026: e21355. doi: 10.1002/advs.202521355.
47. Dai X, Gao Y, Wei W. Post-translational regulations of PD-L1 and PD-1: mechanisms and opportunities for combined immunotherapy. Semin Cancer Biol, 2022, 85: 246-252.
48. Gao M, Shi J, Xiao X, et al. PD-1 regulation in immune homeostasis and immunotherapy. Cancer Lett, 2024, 588: 216726. doi: 10.1016/j.canlet.2024.216726.
49. LaMarche MJ, Acker M, Argintaru A, et al. Identification of TNO155, an allosteric SHP2 inhibitor for the treatment of cancer. J Med Chem, 2020, 63(22): 13578-13594.
50. Chen X, Keller SJ, Hafner P, et al. Tyrosine phosphatase PTPN11/ SHP2 in solid tumors - bull’s eye for targeted therapy? Front Immunol, 2024, 15: 1340726. doi: 10.3389/fimmu.2024.1340726.
51. Li CW, Lim SO, Chung EM, et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell, 2018, 33(2): 187-201.
52. Zhang Q, Yang Z, Hao X, et al. Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling. Cell Biosci, 2023, 13(1): 192. doi: 10.1186/s13578-023-01137-w.
53. Huang HC, Lai YJ, Liao CC, et al. Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro. EBioMedicine, 2021, 74: 103712. doi: 10.1016/j.ebiom.2021.103712.
54. Miao YR, Thakkar KN, Qian J, et al. Neutralization of PD-L2 is essential for overcoming immune checkpoint blockade resistance in ovarian cancer. Clin Cancer Res, 2021, 27(15): 4435-4448.
55. Madhukar G, Haque MA, Khan S, et al. E3 ubiquitin ligases and their therapeutic potential in disease management. Biochem Pharmacol, 2025, 236: 116875. doi: 10.1016/j.bcp.2025.116875.
56. Zhang H, Zhang Y, Feng Z, et al. Discovery of novel proteolysis-targeting chimera molecules as degraders of programmed cell death-ligand 1 for breast cancer therapy. J Med Chem, 2024, 67(13): 10589-10600.
57. Dai MY, Shi YY, Wang AJ, et al. High-potency PD-1/PD-L1 degradation induced by Peptide-PROTAC in human cancer cells. Cell Death Dis, 2022, 13(11): 924. doi: 10.1038/s41419-022-05375-7.
58. Sun C, Liu S, Lau JW, et al. Enzyme-activated orthogonal proteolysis chimeras for tumor microenvironment-responsive immunomodulation. Angew Chem Int Ed Engl, 2025, 64(22): e202423057. doi: 10.1002/anie.202423057.
59. Diao H, Chen J, Zhang Y, et al. BRD4 orchestrates the metabolic-epigenetic regulation of GM-CSF expression and secretion to drive PD-L1+ macrophage-mediated immune evasion in triple-negative breast cancer. Oncogene, 2026, 45(9): 856-874.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress of post-translational modifications of programmed death-1 in tumor immunotherapy

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