1. Brunet, J.-F. et al. A new member of the immunoglobulin superfamily-CTLA-4. Nature 328, 267 (1987).
2. Brunner, M. C. et al. CTLA-4-Mediated inhibition of early events of T cell proliferation. Journal of Immunology 162, 5813-5820 (1999).
3. Linsley, P. S. et al. CTLA-4 is a second receptor for the B cell activation antigen B7. Journal of Experimental Medicine 174, 561-569 (1991).
4. Merwe, P. A. et al. CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. Journal of Experimental Medicine 185, 393-403 (1997).
5. Oosterwegel, M. A. et al. CTLA-4 and T cell activation. Current Opinion in Immunology 11, 294-300 (1999).
6. Kajsa, W. et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271-275 (2008).
7. Leach, D. R. et al. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734-1736 (1996).
8. Korman, A. J. et al. Checkpoint Blockade in Cancer Immunotherapy. Advances in Immunology 90, 297-339 (2006).
9. Camacho, L. H. Novel therapies targeting the immune system: CTLA4 blockade with tremelimumab (CP-675,206), a fully human monoclonal antibody. Expert Opin Investig Drugs 17, 371-385 (2008).
10. Ramagopal, U. A. et al. Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab. Proceedings of the National Academy of Sciences 114, E4223-E4232 (2017).
11. He, M. et al. Remarkably similar CTLA-4 binding properties of therapeutic ipilimumab and tremelimumab antibodies. Oncotarget 8, 67129-67139 (2017).
12. Lee, J. Y. et al. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nature Communications 7, 13354-13354 (2016).
13. Ha, D. et al. Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody. Proceedings of the National Academy of Sciences 116, 609-618 (2019).
14. Bulliard, Y. et al. Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. Journal of Experimental Medicine 210, 1685-1693 (2013).
15. Simpson, T. R. et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma. Journal of Experimental Medicine 210, 1695-1710 (2013).
16. Selby, M. J. et al. Anti-CTLA-4 Antibodies of IgG2a Isotype Enhance Antitumor Activity through Reduction of Intratumoral Regulatory T Cells. Cancer Immunol Res 1, 32-42 (2013).
17. Vargas, F. A. et al. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies. Cancer Cell 33, 649-663. e644 (2018).
18. Ingram, J. R. et al. Anti–CTLA-4 therapy requires an Fc domain for efficacy. Proceedings of the National Academy of Sciences of the United States of America 115, 3912-3917 (2018).
19. Gao, H. et al. Structure of CTLA-4 complexed with a pH-sensitive cancer immunotherapeutic antibody. Cell Discovery 6, 79 (2020).
20. Du, X. et al. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res 28, 1-17 (2018).
21. Chao, Y. et al. Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering. Journal of Biological Chemistry 286, 6685-6696 (2011).
22. Chuang, E. et al. Interaction of CTLA-4 with the Clathrin-Associated Protein AP50 Results in Ligand-Independent Endocytosis That Limits Cell Surface Expression. Journal of Immunology 159, 144-151 (1997).
23. Qureshi, O. S. et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332, 600-603 (2011).
24. Najjar, Y. G. et al. Melanoma antigen-specific effector T cell cytokine secretion patterns in patients treated with ipilimumab. Journal of translational medicine 15, 39 (2017).
25. Clynes, R. A. et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Medicine 6, 443-446 (2000).
26. Stewart, R. et al. The role of Fc gamma receptors in the activity of immunomodulatory antibodies for cancer. Journal for Immunotherapy of Cancer 2, 29 (2014).
27. Romano, E. et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc Natl Acad Sci U S A 112, 6140-6145 (2015).
28. Sharma, A. et al. Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers. Clinical Cancer Research 25, 1233-1238 (2019).
29. Togashi, Y. et al. Regulatory T cells in cancer immunosuppression-implications for anticancer therapy. Nature Reviews Clinical Oncology, 1 (2019).
30. De Simone, M. et al. Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating T regulatory cells. Immunity 45, 1135-1147 (2016).
31. Walker, L. S. et al. Confusing signals: recent progress in CTLA-4 biology. Trends in immunology 36, 63-70 (2015).
32. Linsley, P. S. et al. Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement. Immunity 4, 535-543 (1996).
33. Hye Sun, K. et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 345, 1623-1627 (2014).
34. Desirée, S. et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nature Medicine 20, 1410-1416 (2014).
35. Fecher, L. A. et al. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist 18, 733-743 (2013).
36. Giacomo, A. M. D. et al. The Emerging Toxicity Profiles of Anti–CTLA-4 Antibodies Across Clinical Indications. Seminars in Oncology 37, 499-507 (2010).
37. Horvat, T. Z. et al. Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. Journal of Clinical Oncology 33, 3193-3198 (2015).
38. Zhang, Y. et al. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Research, 1 (2019).
39. Pardon, E. et al. A general protocol for the generation of Nanobodies for structural biology. Nature protocols 9, 674 (2014).
40. L’Abbé, D. et al. Transient Gene Expression in Suspension HEK293-EBNA1 Cells: Methods and Protocols. (2018).
41. Collaborative, C. P. The CCP4 suite: programs for protein crystallography. Acta crystallographica. Section D, Biological crystallography 50, 760 (1994).
42. Storoni, L. C. et al. Likelihood-enhanced fast rotation functions. Acta Crystallographica Section D: Biological Crystallography 60, 432-438 (2004).
43. Emsley, P. et al. Coot: model-building tools for molecular graphics. Acta Crystallographica Section D: Biological Crystallography 60, 2126-2132 (2004).
44. Winn, M. et al. Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallographica Section D: Biological Crystallography 57, 122-133 (2001).
45. Krissinel, E. et al. Inference of Macromolecular Assemblies from Crystalline State. Journal of Molecular Biology 372, 774-797 (2007).
46. Schrodinger, L. The PyMOL molecular graphics system. Version 1, 0 (2010).
47. Waight, J. D. et al. Cutting edge: epigenetic regulation of Foxp3 defines a stable population of CD4+ regulatory T cells in tumors from mice and humans. The Journal of Immunology 194, 878-882 (2015).