R.L. Siegel, T.B. Kratzer, A.N. Giaquinto, H. Sung, A. Jemal, Cancer statistics, 2025. CA: Cancer J. Clin. 75(1), 10–45 (2025)

Google Scholar 

L. Horn, D.R. Spigel, E.E. Vokes, E. Holgado, N. Ready, M. Steins et al., Nivolumab versus Docetaxel in Previously treated patients with advanced non-small-cell lung cancer: two-year Outcomes from Two Randomized, open-label, Phase III trials (CheckMate 017 and CheckMate 057). J. Clin. Oncol. 35(35), 3924–3933 (2017)

Article  CAS  PubMed  PubMed Central  Google Scholar 

M. Zhang, C. Liu, J. Tu, M. Tang, M. Ashrafizadeh, N. Nabavi et al., Advances in cancer immunotherapy: historical perspectives, current developments, and future directions. Mol. Cancer. 24(1), 136 (2025)

Article  PubMed  PubMed Central  Google Scholar 

J. Tang, L. Pearce, J. O’Donnell-Tormey, V.M. Hubbard-Lucey, Trends in the global immuno-oncology landscape. Nat. Rev. Drug. Discov. (2018)

W. Zou, Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer. 5(4), 263–274 (2005)

Article  CAS  PubMed  Google Scholar 

P.A. Mayes, K.W. Hance, A. Hoos, The promise and challenges of immune agonist antibody development in cancer. Nat. Rev. Drug. Discov. 17(7), 509–527 (2018)

Article  CAS  PubMed  Google Scholar 

P. Sharma, J.P. Allison, The future of immune checkpoint therapy. Sci. (New Y., NY) 348(6230), 56–61 (2015)

Article  CAS  Google Scholar 

J. Zhang, F. Dang, J. Ren, W. Wei, Biochemical aspects of PD-L1 regulation in cancer immunotherapy. Trends. Biochem. Sci. 43(12), 1014–1032 (2018)

Article  CAS  PubMed  PubMed Central  Google Scholar 

M.E. Keir, M.J. Butte, G.J. Freeman, A.H. Sharpe, PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 26, 677–704 (2008)

Article  CAS  PubMed  PubMed Central  Google Scholar 

L. Chen, X. Han, Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J. Clin. Investigation 125(9), 3384–3391 (2015)

Article  Google Scholar 

Y. Ishida, y. Agata, Shibahara K, T. Honjo, Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. 0261–4189 (Print

Y. Latchman, C.R. Wood, T. Chernova, D. Chaudhary, M. Borde, I. Chernova et al., PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2(3), 261–268 (2001)

Article  CAS  PubMed  Google Scholar 

L.M. Francisco, P.T. Sage, A.H. Sharpe, The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 236, 219–242 (2010)

Article  CAS  PubMed  PubMed Central  Google Scholar 

W. Zou, J.D. Wolchok, L. Chen, PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 8(328), 328rv4 (2016)

G.J. Freeman, Y. Long Aj, Iwai, K., Bourque, T. ,Chernova, H. ,Nishimura, L.J. Fitz et al., Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. (0022-1007 (Print

H. Dong, S.E. Strome, D.R. Salomao, H. Tamura, F. Hirano, D.B. Flies et al., Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8(8), 793–800 (2002)

Article  CAS  PubMed  Google Scholar 

F. Hirano, K. Kaneko, H. Tamura, H. Dong, S. Wang, M. Ichikawa et al., Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer. Res. 65(3), 1089–1096 (2005)

Article  CAS  PubMed  Google Scholar 

S.L. Topalian, J.M. Taube, D.M. Pardoll, Neoadjuvant checkpoint blockade for cancer immunotherapy. Sci. (New Y., NY) 367, 6477 (2020)

Google Scholar 

H. Kuipers, F. Muskens, M. Willart, D. Hijdra, V.A. Fb, C. Aj, H. Hc et al., Contribution of the PD-1 ligands/PD-1 signaling pathway to dendritic cell-mediated CD4+ T cell activation. 0014–2980

A.A. Davis, V.G. Patel, The role of PD-L1 expression as a predictive biomarker: an analysis of all US food and drug administration (FDA) approvals of immune checkpoint inhibitors. J. Immunother. Cancer. 7(1), 278 (2019)

Article  PubMed  PubMed Central  Google Scholar 

G. Köhler,C. Milstein, Continuous cultures of fused cells secreting antibody of predefined specificity. 0028–0836 (Print)

A. Ribas, J.D. Wolchok, Cancer immunotherapy using checkpoint blockade. Sci. (New Y., NY) 359(6382), 1350–1355 (2018)

Article  CAS  Google Scholar 

A.D. Waldman, J.M. Fritz, M.J. Lenardo, A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20(11), 651–668 (2020)

Article  CAS  PubMed  PubMed Central  Google Scholar 

A. Jw, P. Lu,P. Majumder, Ahmed, F.-B. Jm, B. Jm, STAT3, STAT4, NFATc1, and CTCF regulate PD-1 through multiple novel regulatory regions in murine T cells. (1550-6606) Electronic))

M.M. Staron, S.M. Gray, H.D. Marshall, I.A. Parish, J.H. Chen, C.J. Perry et al., The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8(+) T cells during chronic infection. Immunity 41(5), 802–814 (2014)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S. Terawaki, S. Chikuma, S. Shibayama, T. Hayashi, T. Yoshida, T. Okazaki et al., IFN-alpha directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. The. J. Immunol. 186(5), 2772–2779 (2011)

Article  CAS  PubMed  Google Scholar 

M. Mathieu, N. Cotta-Grand, J.F. Daudelin, P. Thebault, N. Labrecque, Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunol. Cell. Biol. 91(1), 82–88 (2013)

Article  CAS  PubMed  Google Scholar 

C. Kao, K.J. Oestreich, M.A. Paley, A. Crawford, J.M. Angelosanto, M.A. Ali et al., Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nat. Immunol. 12(7), 663–671 (2011)

Article  CAS  PubMed  PubMed Central  Google Scholar 

P. Lu, B.A. Youngblood, J.W. Austin, A.U. Mohammed, R. Butler, R. Ahmed et al., Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. J. Exp. Med. 211(3), 515–527 (2014)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S.D. Blackburn, H. Shin, W.N. Haining, T. Zou, C.J. Workman, A. Polley et al., Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10(1), 29–37 (2009)

Article  CAS  PubMed  Google Scholar 

S. Liu, J. Ren, P. Ten Dijke, Targeting TGFβ signal transduction for cancer therapy. Signal. Transduct. Target. Ther. 6(1), 8 (2021)

Article  PubMed  PubMed Central  Google Scholar 

B.V. Park, Z.T. Freeman, A. Ghasemzadeh, M.A. Chattergoon, A. Rutebemberwa, J. Steigner et al., TGFbeta1-mediated SMAD3 enhances PD-1 expression on antigen-specific T cells in cancer. Cancer Discov. 6(12), 1366–1381 (2016)

Article  CAS  PubMed  PubMed Central  Google Scholar 

P. Wu, B. Geng, Q. Chen, E. Zhao, J. Liu, C. Sun et al., Tumor cell-derived TGFbeta1 attenuates antitumor immune activity of T cells via regulation of PD-1 mRNA. Cancer. Immunol. Res. 8(12), 1470–1484 (2020)

Article  CAS  PubMed  Google Scholar 

X. Wang, Q. He, H. Shen, A. Xia, W. Tian, W. Yu et al., TOX promotes the exhaustion of antitumor CD8(+) T cells by preventing PD1 degradation in hepatocellular carcinoma. J. Educ. Chang. Hepatol. 71(4), 731–741 (2019)

Article  CAS  Google Scholar 

J. Arranz-Nicolas, M. Martin-Salgado, C. Rodriguez-Rodriguez, R. Liebana, M.C. Moreno-Ortiz, J. Leitner et al., Diacylglycerol kinase zeta limits IL-2-dependent control of PD-1 expression in tumor-infiltrating T lymphocytes. J. Immunother. Cancer. 8(2. 2020)

J. Wang, L. Yan, X. Wang, R. Jia, J. Guo, Surface PD-1 expression in T cells is suppressed by HNRNPK through an exonic splicing silencer on exon 3. Inflamm. Res.: Off. J. The. Eur. Histamine Res. Soc. [Et Al] 73(7), 1123–1135 (2024)

Article  Google Scholar 

S. Kumagai, S. Koyama, K. Itahashi, T. Tanegashima, Y.T. Lin, Y. Togashi et al., Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer. Cell. 40(2), 201–18.e9 (2022)

Article  CAS  PubMed  Google Scholar 

T. Montecchi, G. Nannini, D. De Tommaso, C. Cassioli, F. Coppola, M.N. Ringressi et al., Human colorectal cancer: upregulation of the adaptor protein Rai in TILs leads to cell dysfunction by sustaining GSK-3 activation and PD-1 expression. Cancer. Immunol. Immunother. 73(1), 2 (2024)

Article  CAS