Modulation of N-glycosylation in the PD-1: PD-L1 axis as a strategy to enhance cancer immunotherapies

被引：0
作者：
Granica, Monika [1 ,2 ,3 ]
Laskowski, Gustaw [2 ]
Link-Lenczowski, Pawel [4 ,5 ]
Graczyk-Jarzynka, Agnieszka [2 ]
机构：
[1] Med Univ Warsaw, Dept Immunol, PL-02097 Warsaw, Poland
[2] Polish Acad Sci, Dept Immunol, Mossakowski Med Res Inst, PL-02106 Warsaw, Poland
[3] Med Univ Warsaw, Doctoral Sch, PL-02091 Warsaw, Poland
[4] Jagiellonian Univ Med Coll, Fac Hlth Sci, Dept Med Physiol, PL-31126 Krakow, Poland
[5] Jagiellonian Univ Med Coll, Ctr Dev Therapies Civilizat & Age Related Dis, PL-31066 Krakow, Poland
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2025年 / 1880卷 / 02期
关键词：
Immunotherapy; PD-L1; PD-1; PD-L2; N-glycosylation; Checkpoints; CELL CARCINOMA; B7; FAMILY; EXPRESSION; MEMBER; MICROENVIRONMENT; BLOCKADE; RECEPTOR; PATHWAY; EVASION;
D O I：
10.1016/j.bbcan.2025.189274
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The modulation of the N-glycosylation status in immune checkpoints, particularly the PD-1/PD-L1 axis, has emerged as a promising approach to enhance cancer immunotherapies. While immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have achieved significant clinical success, recent studies highlight the critical role ofNglycosylation in regulating their expression, stability, and function. Alterations in N-glycosylation might affect the efficacy of ICIs by modulating the interactions between immune checkpoints and antibodies used in therapy. This review focuses on the glycosylation of PD-1 and its ligands PD-L1 and PD-L2, examining how Nglycans influence immune responses and contribute to immune evasion by tumors. It explores innovative strategies to modulate glycosylation in tumor and immune cells, including the use ofNglycosylation inhibitors and novel genetic manipulation techniques. Understanding the interplay betweenNglycosylation and immune checkpoint functions is essential for optimizing immunotherapy outcomes and overcoming therapeutic resistance in cancer patients.
引用
收藏
页数：9
相关论文
共 83 条
[1]  
Reck M., Remon J., Hellmann M.D., First-line immunotherapy for non–small-cell lung cancer, J. Clin. Oncol., 40, pp. 586-597, (2022)
[2]  
Patil V.M., Noronha V., Menon N., Rai R., Bhattacharjee A., Singh A., Nawale K., Jogdhankar S., Tambe R., Dhumal S., Sawant R., Alone M., Karla D., Peelay Z., Pathak S., Balaji A., Kumar S., Purandare N., Agarwal A., Puranik A., Mahajan A., Janu A., Kumar Singh G., Mittal N., Yadav S., Banavali S., Prabhash K., Low-dose immunotherapy in head and neck cancer: a randomized study, J. Clin. Oncol., 41, pp. 222-232, (2022)
[3]  
Geng Q., Jiao P., Anti-PD-L1-based bispecific antibodies targeting co-inhibitory and co-stimulatory molecules for cancer immunotherapy, Molecules, 29, (2024)
[4]  
Li T., Niu M., Zhou J., Wu K., Yi M., The enhanced antitumor activity of bispecific antibody targeting PD-1 / PD-L1 signaling, Cell Commun. Signal., 22, pp. 1-18, (2024)
[5]  
Bajor M., Graczyk-Jarzynka A., Marhelava K., Burdzinska A., Muchowicz A., Goral A., Zhylko A., Soroczynska K., Retecki K., Krawczyk M., Klopotowska M., Pilch Z., Paczek L., Malmberg K.J., Walchli S., Winiarska M., Zagozdzon R., PD-L1 CAR effector cells induce self-amplifying cytotoxic effects against target cells, J. Immunother. Cancer, 10, (2022)
[6]  
Li C.W., Lim S.O., Xia W., Lee H.H., Chan L.C., Kuo C.W., Khoo K.H., Chang S.S., Cha J.H., Kim T., Hsu J.L., Wu Y., Hsu J.M., Yamaguchi H., Ding Q., Wang Y., Yao J., Lee C.C., Wu H.J., Sahin A.A., Allison J.P., Yu D., Hortobagyi G.N., Hung M.C., Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity, Nat. Commun., 7, pp. 1-11, (2016)
[7]  
Lin Y., Lubman D.M., The role of N-glycosylation in cancer, Acta Pharm. Sin. B, 14, pp. 1098-1110, (2024)
[8]  
Zhang R., Yang Y., Dong W., Lin M., He J., Zhang X., Tian T., Yang Y., Chen K., Lei Q.Y., Zhang S., Xu Y., Lv L., D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1, Proc. Natl. Acad. Sci. USA, 119, pp. 1-12, (2022)
[9]  
Greco B., Malacarne V., DeGirardi F., Scotti G.M., Manfredi F., Angelino E., Sirini C., Camisa B., Falcone L., Moresco M.A., Paolella K., Di Bono M., Norata R., Sanvito F., Arcangeli S., Doglioni C., Ciceri F., Bonini C., Graziani A., Bondanza A., Casucci M., Disrupting N-glycan expression on tumor cells boosts chimeric antigen receptor T cell efficacy against solid malignancies, Sci. Transl. Med., 14, (2022)
[10]  
Lu D., Xu Z., Zhang D., Jiang M., Liu K., He J., PD-1 N58-glycosylation-dependent binding of monoclonal antibody cemiplimab for immune checkpoint therapy, Front. Immunol., 13, pp. 1-11, (2022)
123456789