References

1. Waldman, A.D.; Fritz, J.M.; Lenardo, M.J. A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice. Nat. Rev. Immunol. 2020, 20, 651–668.
2. Emens, L.A.; Ascierto, P.A.; Darcy, P.K.; Demaria, S.; Eggermont, A.M.M.; Redmond, W.L.; Seliger, B.; Marincola, F.M. Cancer Immunotherapy: Opportunities and Challenges in the Rapidly Evolving Clinical Landscape. Eur. J. Cancer 2017, 81, 116–129.
3. Fife, B.T.; Bluestone, J.A. Control of Peripheral T-Cell Tolerance and Autoimmunity via the CTLA-4 and PD-1 Pathways. Immunol. Rev. 2008, 224, 166–182.
4. Decker, W.K.; da Silva, R.F.; Sanabria, M.H.; Angelo, L.S.; Guimarães, F.; Burt, B.M.; Kheradmand, F.; Paust, S. Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models. Front. Immunol. 2017, 8, 829.
5. Tundo, G.R.; Sbardella, D.; Lacal, P.M.; Graziani, G.; Marini, S. On the Horizon: Targeting Next-Generation Immune Checkpoints for Cancer Treatment. Chemotherapy 2019, 64, 62–80.
6. Fritz, J.M.; Lenardo, M.J. Development of Immune Checkpoint Therapy for Cancer. J. Exp. Med. 2019, 216, 1244–1254.
7. Kumar, V.; Chaudhary, N.; Garg, M.; Floudas, C.S.; Soni, P.; Chandra, A.B. Current Diagnosis and Management of Immune Related Adverse Events (IrAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front. Pharm. 2017, 8, 49.
8. Wang, S.; He, Z.; Wang, X.; Li, H.; Liu, X.-S. Antigen Presentation and Tumor Immunogenicity in Cancer Immunotherapy Response Prediction. Elife 2019, 8, e49020.
9. Chowell, D.; Morris, L.G.T.; Grigg, C.M.; Weber, J.K.; Samstein, R.M.; Makarov, V.; Kuo, F.; Kendall, S.M.; Requena, D.; Riaz, N.; et al. Patient HLA Class I Genotype Influences Cancer Response to Checkpoint Blockade Immunotherapy. Science 2018, 359, 582–587.
10. Zaretsky, J.M.; Garcia-Diaz, A.; Shin, D.S.; Escuin-Ordinas, H.; Hugo, W.; Hu-Lieskovan, S.; Torrejon, D.Y.; Abril-Rodriguez, G.; Sandoval, S.; Barthly, L.; et al. Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. Available online: https://www.nejm.org/doi/10.1056/NEJMoa1604958 (accessed on 21 June 2021).
11. Labani-Motlagh, A.; Ashja-Mahdavi, M.; Loskog, A. The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses. Front. Immunol. 2020, 11, 940.
12. Gubin, M.M.; Zhang, X.; Schuster, H.; Caron, E.; Ward, J.P.; Noguchi, T.; Ivanova, Y.; Hundal, J.; Arthur, C.D.; Krebber, W.-J.; et al. Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens. Nature 2014, 515, 577–581.
13. Seliger, B.; Maeurer, M.J.; Ferrone, S. Antigen-Processing Machinery Breakdown and Tumor Growth. Immunol. Today 2000, 21, 455–464.
14. Vizcaíno, J.A.; Kubiniok, P.; Kovalchik, K.A.; Ma, Q.; Duquette, J.D.; Mongrain, I.; Deutsch, E.W.; Peters, B.; Sette, A.; Sirois, I.; et al. The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases. Mol. Cell Proteom. 2020, 19, 31–49.
15. Tundo, G.R.; Sbardella, D.; Santoro, A.M.; Coletta, A.; Oddone, F.; Grasso, G.; Milardi, D.; Lacal, P.M.; Marini, S.; Purrello, R.; et al. The Proteasome as a Druggable Target with Multiple Therapeutic Potentialities: Cutting and Non-Cutting Edges. Pharm. Ther. 2020, 213, 107579.
16. Cascio, P. PA28γ: New Insights on an Ancient Proteasome Activator. Biomolecules 2021, 11, 228.
17. Sala, A.J.; Bott, L.C.; Morimoto, R.I. Shaping Proteostasis at the Cellular, Tissue, and Organismal Level. J. Cell Biol. 2017, 216, 1231–1241.
18. Klaips, C.L.; Jayaraj, G.G.; Hartl, F.U. Pathways of Cellular Proteostasis in Aging and Disease. J. Cell Biol. 2018, 217, 51–63.
19. Kudriaeva, A.A.; Sokolov, A.V.; Belogurov, A.A.J. Stochastics of Degradation: The Autophagic-Lysosomal System of the Cell. Acta Nat. 2020, 12, 18–32.
20. Kudriaeva, A.; Kuzina, E.S.; Zubenko, O.; Smirnov, I.V.; Belogurov, A. Charge-Mediated Proteasome Targeting. FASEB J. 2019, 33, 6852–6866.
21. Glickman, M.H.; Ciechanover, A. The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction. Physiol Rev. 2002, 82, 373–428.
22. Kunjappu, M.J.; Hochstrasser, M. Assembly of the 20S Proteasome. Biochim. Biophys. Acta 2014, 1843, 2–12.
23. Lander, G.C.; Estrin, E.; Matyskiela, M.E.; Bashore, C.; Nogales, E.; Martin, A. Complete Subunit Architecture of the Proteasome Regulatory Particle. Nature 2012, 482, 186–191.
24. Scheffner, M.; Nuber, U.; Huibregtse, J.M. Protein Ubiquitination Involving an E1-E2-E3 Enzyme Ubiquitin Thioester Cascade. Nature 1995, 373, 81–83.
25. Leestemaker, Y.; Ovaa, H. Tools to Investigate the Ubiquitin Proteasome System. Drug Discov. Today Technol. 2017, 26, 25–31.
26. Pickart, C.M. Mechanisms Underlying Ubiquitination. Annu. Rev. Biochem. 2001, 70, 503–533.
27. Windheim, M.; Peggie, M.; Cohen, P. Two Different Classes of E2 Ubiquitin-Conjugating Enzymes Are Required for the Mono-Ubiquitination of Proteins and Elongation by Polyubiquitin Chains with a Specific Topology. Biochem. J. 2008, 409, 723–729.
28. Bellia, F.; Lanza, V.; García-Viñuales, S.; Ahmed, I.M.M.; Pietropaolo, A.; Iacobucci, C.; Malgieri, G.; D’Abrosca, G.; Fattorusso, R.; Nicoletti, V.G.; et al. Ubiquitin Binds the Amyloid β Peptide and Interferes with Its Clearance Pathways. Chem. Sci. 2019, 10, 2732–2742.
29. Ciechanover, A. The Unravelling of the Ubiquitin System. Nat. Rev. Mol. Cell Biol. 2015, 16, 322–324.
30. Zheng, N.; Shabek, N. Ubiquitin Ligases: Structure, Function, and Regulation. Annu. Rev. Biochem. 2017, 86, 129–157.
31. Berndsen, C.E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat. Struct. Mol. Biol. 2014, 21, 301–307.
32. Komander, D.; Rape, M. The Ubiquitin Code. Annu. Rev. Biochem. 2012, 81, 203–229.
33. Deshaies, R.J.; Joazeiro, C.A.P. RING Domain E3 Ubiquitin Ligases. Annu. Rev. Biochem. 2009, 78, 399–434.
34. Kudriaeva, A.A.; Livneh, I.; Baranov, M.S.; Ziganshin, R.H.; Tupikin, A.E.; Zaitseva, S.O.; Kabilov, M.R.; Ciechanover, A.; Belogurov, A.A., Jr. In-depth characterization of ubiquitin turnover in mammalian cells by fluorescence tracking. Cell Chem. Biol. 2021, 28, 1192–1205.e9.
35. Yuan, T.; Yan, F.; Ying, M.; Cao, J.; He, Q.; Zhu, H.; Yang, B. Inhibition of Ubiquitin-Specific Proteases as a Novel Anticancer Therapeutic Strategy. Front. Pharm. 2018, 9, 1080.
36. Oikawa, D.; Sato, Y.; Ito, H.; Tokunaga, F. Linear Ubiquitin Code: Its Writer, Erasers, Decoders, Inhibitors, and Implications in Disorders. Int. J. Mol. Sci 2020, 21, 3381.
37. Pfoh, R.; Lacdao, I.K.; Saridakis, V. Deubiquitinases and the New Therapeutic Opportunities Offered to Cancer. Endocr. Relat. Cancer 2015, 22, T35–T54.
38. Martinez, C.K.; Monaco, J.J. Homology of Proteasome Subunits to a Major Histocompatibility Complex-Linked LMP Gene. Nature 1991, 353, 664–667.
39. Rock, K.L.; Gramm, C.; Rothstein, L.; Clark, K.; Stein, R.; Dick, L.; Hwang, D.; Goldberg, A.L. Inhibitors of the Proteasome Block the Degradation of Most Cell Proteins and the Generation of Peptides Presented on MHC Class I Molecules. Cell 1994, 78, 761–771.
40. Aki, M.; Shimbara, N.; Takashina, M.; Akiyama, K.; Kagawa, S.; Tamura, T.; Tanahashi, N.; Yoshimura, T.; Tanaka, K.; Ichihara, A. Interferon-Gamma Induces Different Subunit Organizations and Functional Diversity of Proteasomes. J. Biochem. 1994, 115, 257–269.
41. Boes, B.; Hengel, H.; Ruppert, T.; Multhaup, G.; Koszinowski, U.H.; Kloetzel, P.M. Interferon Gamma Stimulation Modulates the Proteolytic Activity and Cleavage Site Preference of 20S Mouse Proteasomes. J. Exp. Med. 1994, 179, 901–909.
42. Driscoll, J.; Brown, M.G.; Finley, D.; Monaco, J.J. MHC-Linked LMP Gene Products Specifically Alter Peptidase Activities of the Proteasome. Nature 1993, 365, 262–264.
43. Gaczynska, M.; Rock, K.L.; Goldberg, A.L. Role of Proteasomes in Antigen Presentation. Enzym. Protein 1993, 47, 354–369.
44. Griffin, T.A.; Nandi, D.; Cruz, M.; Fehling, H.J.; Kaer, L.V.; Monaco, J.J.; Colbert, R.A. Immunoproteasome Assembly: Cooperative Incorporation of Interferon Gamma (IFN-Gamma)-Inducible Subunits. J. Exp. Med. 1998, 187, 97–104.
45. Groettrup, M.; Standera, S.; Stohwasser, R.; Kloetzel, P.M. The Subunits MECL-1 and LMP2 Are Mutually Required for Incorporation into the 20S Proteasome. Proc. Natl. Acad. Sci. USA 1997, 94, 8970–8975.
46. Morozov, A.V.; Karpov, V.L. Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer. Front. Oncol. 2019, 9, 761.
47. Tanaka, K. Role of Proteasomes Modified by Interferon-Gamma in Antigen Processing. J. Leukoc Biol. 1994, 56, 571–575.
48. Heink, S.; Ludwig, D.; Kloetzel, P.-M.; Krüger, E. IFN-Gamma-Induced Immune Adaptation of the Proteasome System Is an Accelerated and Transient Response. Proc. Natl. Acad. Sci. USA 2005, 102, 9241–9246.
49. Guillaume, B.; Chapiro, J.; Stroobant, V.; Colau, D.; Van Holle, B.; Parvizi, G.; Bousquet-Dubouch, M.-P.; Théate, I.; Parmentier, N.; Van den Eynde, B.J. Two Abundant Proteasome Subtypes That Uniquely Process Some Antigens Presented by HLA Class I Molecules. Proc. Natl. Acad. Sci. USA 2010, 107, 18599–18604.
50. Khan, S.; van den Broek, M.; Schwarz, K.; de Giuli, R.; Diener, P.A.; Groettrup, M. Immunoproteasomes Largely Replace Constitutive Proteasomes during an Antiviral and Antibacterial Immune Response in the Liver. J. Immunol. 2001, 167, 6859–6868.
51. Groettrup, M.; Kirk, C.J.; Basler, M. Proteasomes in Immune Cells: More than Peptide Producers? Nat. Rev. Immunol. 2010, 10, 73–78.
52. Reis, J.; Guan, X.Q.; Kisselev, A.F.; Papasian, C.J.; Qureshi, A.A.; Morrison, D.C.; Van Way, C.W.; Vogel, S.N.; Qureshi, N. LPS-Induced Formation of Immunoproteasomes: TNF-α and Nitric Oxide Production Are Regulated by Altered Composition of Proteasome-Active Sites. Cell Biochem. Biophys. 2011, 60, 77–88.
53. Shin, E.-C.; Seifert, U.; Kato, T.; Rice, C.M.; Feinstone, S.M.; Kloetzel, P.-M.; Rehermann, B. Virus-Induced Type I IFN Stimulates Generation of Immunoproteasomes at the Site of Infection. J. Clin. Investig. 2006, 116, 3006–3014.
54. Johnston-Carey, H.K.; Pomatto, L.C.D.; Davies, K.J.A. The Immunoproteasome in Oxidative Stress, Aging, and Disease. Crit Rev. Biochem Mol. Biol. 2015, 51, 268–281.
55. Höhn, T.J.A.; Grune, T. The Proteasome and the Degradation of Oxidized Proteins: Part III-Redox Regulation of the Proteasomal System. Redox Biol. 2014, 2, 388–394.
56. Vigneron, N.; Abi Habib, J.; Van den Eynde, B.J. Learning from the Proteasome How to Fine-Tune Cancer Immunotherapy. Trends Cancer 2017, 3, 726–741.
57. Huber, E.M.; Basler, M.; Schwab, R.; Heinemeyer, W.; Kirk, C.J.; Groettrup, M.; Groll, M. Immuno- and Constitutive Proteasome Crystal Structures Reveal Differences in Substrate and Inhibitor Specificity. Cell 2012, 148, 727–738.
58. Akiyama, K.; Kagawa, S.; Tamura, T.; Shimbara, N.; Takashina, M.; Kristensen, P.; Hendil, K.B.; Tanaka, K.; Ichihara, A. Replacement of Proteasome Subunits X and Y by LMP7 and LMP2 Induced by Interferon-Gamma for Acquirement of the Functional Diversity Responsible for Antigen Processing. FEBS Lett. 1994, 343, 85–88.
59. Kniepert, A.; Groettrup, M. The Unique Functions of Tissue-Specific Proteasomes. Trends. Biochem. Sci. 2014, 39, 17–24.
60. Platteel, A.C.M.; Liepe, J.; van Eden, W.; Mishto, M.; Sijts, A.J.A.M. An Unexpected Major Role for Proteasome-Catalyzed Peptide Splicing in Generation of T Cell Epitopes: Is There Relevance for Vaccine Development? Front. Immunol. 2017, 8, 1441.
61. Vigneron, N.; Ferrari, V.; Stroobant, V.; Abi Habib, J.; Van den Eynde, B.J. Peptide Splicing by the Proteasome. J. Biol. Chem. 2017, 292, 21170–21179.
62. Vigneron, N.; Stroobant, V.; Chapiro, J.; Ooms, A.; Degiovanni, G.; Morel, S.; van der Bruggen, P.; Boon, T.; Van den Eynde, B.J. An Antigenic Peptide Produced by Peptide Splicing in the Proteasome. Science 2004, 304, 587–590.
63. Liepe, J.; Marino, F.; Sidney, J.; Jeko, A.; Bunting, D.E.; Sette, A.; Kloetzel, P.M.; Stumpf, M.P.H.; Heck, A.J.R.; Mishto, M. A Large Fraction of HLA Class I Ligands Are Proteasome-Generated Spliced Peptides. Science 2016, 354, 354–358.
64. Morel, S.; Lévy, F.; Burlet-Schiltz, O.; Brasseur, F.; Probst-Kepper, M.; Peitrequin, A.L.; Monsarrat, B.; Van Velthoven, R.; Cerottini, J.C.; Boon, T.; et al. Processing of Some Antigens by the Standard Proteasome but Not by the Immunoproteasome Results in Poor Presentation by Dendritic Cells. Immunity 2000, 12, 107–117.
65. Chapiro, J.; Claverol, S.; Piette, F.; Ma, W.; Stroobant, V.; Guillaume, B.; Gairin, J.-E.; Morel, S.; Burlet-Schiltz, O.; Monsarrat, B.; et al. Destructive Cleavage of Antigenic Peptides Either by the Immunoproteasome or by the Standard Proteasome Results in Differential Antigen Presentation. J. Immunol. 2006, 176, 1053–1061.
66. Kincaid, E.Z.; Che, J.W.; York, I.; Escobar, H.; Reyes-Vargas, E.; Delgado, J.C.; Welsh, R.M.; Karow, M.L.; Murphy, A.J.; Valenzuela, D.M.; et al. Mice Completely Lacking Immunoproteasomes Show Major Changes in Antigen Presentation. Nat. Immunol. 2011, 13, 129–135.
67. Van Kaer, L.; Ashton-Rickardt, P.G.; Eichelberger, M.; Gaczynska, M.; Nagashima, K.; Rock, K.L.; Goldberg, A.L.; Doherty, P.C.; Tonegawa, S. Altered Peptidase and Viral-Specific T Cell Response in LMP2 Mutant Mice. Immunity 1994, 1, 533–541.
68. de Graaf, N.; van Helden, M.J.G.; Textoris-Taube, K.; Chiba, T.; Topham, D.J.; Kloetzel, P.-M.; Zaiss, D.M.W.; Sijts, A.J.A.M. PA28 and the Proteasome Immunosubunits Play a Central and Independent Role in the Production of MHC Class I-Binding Peptides in Vivo. Eur. J. Immunol. 2011, 41, 926–935.
69. Chapatte, L.; Ayyoub, M.; Morel, S.; Peitrequin, A.-L.; Lévy, N.; Servis, C.; Van den Eynde, B.J.; Valmori, D.; Lévy, F. Processing of Tumor-Associated Antigen by the Proteasomes of Dendritic Cells Controls in Vivo T-Cell Responses. Cancer Res. 2006, 66, 5461–5468.
70. Borissenko, L.; Groll, M. Diversity of proteasomal missions: Fine tuning of the immune response. Biol. Chem. 2007, 388, 947–955.
71. Çetin, G.; Klafack, S.; Studencka-Turski, M.; Krüger, E.; Ebstein, F. The Ubiquitin-Proteasome System in Immune Cells. Biomolecules 2021, 11, 60.
72. Basler, M.; Kirk, C.J.; Groettrup, M. The Immunoproteasome in Antigen Processing and Other Immunological Functions. Curr. Opin. Immunol. 2013, 25, 74–80.
73. Fehling, H.J.; Swat, W.; Laplace, C.; Kühn, R.; Rajewsky, K.; Müller, U.; von Boehmer, H. MHC Class I Expression in Mice Lacking the Proteasome Subunit LMP-7. Science 1994, 265, 1234–1237.
74. McCarthy, M.K.; Weinberg, J.B. The Immunoproteasome and Viral Infection: A Complex Regulator of Inflammation. Front. Microbiol. 2015, 6, 21.
75. de Verteuil, D.; Muratore-Schroeder, T.L.; Granados, D.P.; Fortier, M.-H.; Hardy, M.-P.; Bramoullé, A.; Caron, E.; Vincent, K.; Mader, S.; Lemieux, S.; et al. Deletion of Immunoproteasome Subunits Imprints on the Transcriptome and Has a Broad Impact on Peptides Presented by Major Histocompatibility Complex I Molecules. Mol. Cell Proteom. 2010, 9, 2034–2047.
76. Basler, M.; Youhnovski, N.; Van Den Broek, M.; Przybylski, M.; Groettrup, M. Immunoproteasomes Down-Regulate Presentation of a Subdominant T Cell Epitope from Lymphocytic Choriomeningitis Virus. J. Immunol. 2004, 173, 3925–3934.
77. Zanker, D.; Waithman, J.; Yewdell, J.W.; Chen, W. Mixed Proteasomes Function to Increase Viral Peptide Diversity and Broaden Antiviral CD8+ T Cell Responses. J. Immunol. 2013, 191, 52–59.
78. Kloetzel, P.M. Antigen processing by the proteasome. Nat. Rev. Mol. Cell Biol. 2016, 2, 179–188.
79. Tubío-Santamaría, N.; Ebstein, F.; Heidel, F.H.; Krüger, E. Immunoproteasome Function in Normal and Malignant Hematopoiesis. Cells 2021, 10, 1577.
80. Mishto, M.; Liepe, J.; Textoris-Taube, K.; Keller, C.; Henklein, P.; Weberruß, M.; Dahlmann, B.; Enenkel, C.; Voigt, A.; Kuckelkorn, U.; et al. Proteasome Isoforms Exhibit Only Quantitative Differences in Cleavage and Epitope Generation. Eur. J. Immunol. 2014, 44, 3508–3521.
81. Chen, Y.; Zhang, Y.; Guo, X. Proteasome Dysregulation in Human Cancer: Implications for Clinical Therapies. Cancer Metastasis Rev. 2017, 36, 703–716.
82. Algarra, I.; Collado, A.; Garrido, F. Altered MHC Class I Antigens in Tumors. Int. J. Clin. Lab. Res. 1997, 27, 95–102.
83. Tripathi, S.C.; Peters, H.L.; Taguchi, A.; Katayama, H.; Wang, H.; Momin, A.; Jolly, M.K.; Celiktas, M.; Rodriguez-Canales, J.; Liu, H.; et al. Immunoproteasome Deficiency Is a Feature of Non-Small Cell Lung Cancer with a Mesenchymal Phenotype and Is Associated with a Poor Outcome. Proc. Natl. Acad. Sci. USA 2016, 113, E1555–E1564.
84. Heink, S.; Fricke, B.; Ludwig, D.; Kloetzel, P.-M.; Krüger, E. Tumor Cell Lines Expressing the Proteasome Subunit Isoform LMP7E1 Exhibit Immunoproteasome Deficiency. Cancer Res. 2006, 66, 649–652.
85. Fellerhoff, B.; Gu, S.; Laumbacher, B.; Nerlich, A.G.; Weiss, E.H.; Glas, J.; Kopp, R.; Johnson, J.P.; Wank, R. The LMP7-K Allele of the Immunoproteasome Exhibits Reduced Transcript Stability and Predicts High Risk of Colon Cancer. Cancer Res. 2011, 71, 7145–7154.
86. Yang, X.-W.; Wang, P.; Liu, J.-Q.; Zhang, H.; Xi, W.-D.; Jia, X.-H.; Wang, K.-K. Coordinated Regulation of the Immunoproteasome Subunits by PML/RARα and PU.1 in Acute Promyelocytic Leukemia. Oncogene 2014, 33, 2700–2708.
87. Yang, C.; Schmidt, M. Cutting through Complexity: The Proteolytic Properties of Alternate Immunoproteasome Complexes. Chem Biol. 2014, 21, 435–436.
88. Rouette, A.; Trofimov, A.; Haberl, D.; Boucher, G.; Lavallée, V.-P.; D’Angelo, G.; Hébert, J.; Sauvageau, G.; Lemieux, S.; Perreault, C. Expression of Immunoproteasome Genes Is Regulated by Cell-Intrinsic and -Extrinsic Factors in Human Cancers. Sci. Rep. 2016, 6, 34019.
89. Niewerth, D.; Jansen, G.; Assaraf, Y.G.; Zweegman, S.; Kaspers, G.J.L.; Cloos, J. Molecular Basis of Resistance to Proteasome Inhibitors in Hematological Malignancies. Drug Resist. Updat. 2015, 18, 18–35.
90. Vachharajani, N.; Joeris, T.; Luu, M.; Hartmann, S.; Pautz, S.; Jenike, E.; Pantazis, G.; Prinz, I.; Hofer, M.J.; Steinhoff, U.; et al. Prevention of Colitis-Associated Cancer by Selective Targeting of Immunoproteasome Subunit LMP7. Oncotarget 2017, 8, 50447–50459.
91. Weon, J.L.; Potts, P.R. The MAGE Protein Family and Cancer. Curr. Opin. Cell Biol. 2015, 37, 1–8.
92. Olsson, N.; Heberling, M.L.; Zhang, L.; Jhunjhunwala, S.; Phung, Q.T.; Lin, S.; Anania, V.G.; Lill, J.R.; Elias, J.E. An Integrated Genomic, Proteomic, and Immunopeptidomic Approach to Discover Treatment-Induced Neoantigens. Front. Immunol. 2021, 12, 662443.
93. Schumacher, T.N.; Schreiber, R.D. Neoantigens in Cancer Immunotherapy. Science 2015, 348, 69–74.
94. Guillaume, B.; Stroobant, V.; Bousquet-Dubouch, M.-P.; Colau, D.; Chapiro, J.; Parmentier, N.; Dalet, A.; Van den Eynde, B.J. Analysis of the Processing of Seven Human Tumor Antigens by Intermediate Proteasomes. J. Immunol. 2012, 189, 3538–3547.
95. Schooten, E.; Di Maggio, A.; van Bergen En Henegouwen, P.M.P.; Kijanka, M.M. MAGE-A Antigens as Targets for Cancer Immunotherapy. Cancer Treat. Rev. 2018, 67, 54–62.
96. Fabre, B.; Lambour, T.; Garrigues, L.; Ducoux-Petit, M.; Amalric, F.; Monsarrat, B.; Burlet-Schiltz, O.; Bousquet-Dubouch, M.-P. Label-Free Quantitative Proteomics Reveals the Dynamics of Proteasome Complexes Composition and Stoichiometry in a Wide Range of Human Cell Lines. J. Proteome Res. 2014, 13, 3027–3037.
97. Morozov, A.V.; Karpov, V.L. Biological Consequences of Structural and Functional Proteasome Diversity. Heliyon 2018, 4, e00894.
98. Goldberg, A.L.; Gaczynska, M.; Grant, E.; Michalek, M.; Rock, K.L. Functions of the Proteasome in Antigen Presentation. Cold Spring Harb. Symp. Quant. Biol. 1995, 60, 479–490.
99. Fiebiger, B.M.; Pfister, H.; Behrends, U.; Mautner, J. Polyubiquitination of Lysine-48 Is an Essential but Indirect Signal for MHC Class I Antigen Processing. Eur. J. Immunol. 2015, 45, 716–727.
100. Vigneron, N.; Van den Eynde, B.J. Insights into the Processing of MHC Class I Ligands Gained from the Study of Human Tumor Epitopes. Cell Mol. Life Sci. 2011, 68, 1503–1520.
101. Mpakali, A.; Stratikos, E. The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy. Cancers 2021, 13, 134.
102. Turajlic, S.; Litchfield, K.; Xu, H.; Rosenthal, R.; McGranahan, N.; Reading, J.L.; Wong, Y.N.S.; Rowan, A.; Kanu, N.; Al Bakir, M.; et al. Insertion-and-Deletion-Derived Tumour-Specific Neoantigens and the Immunogenic Phenotype: A Pan-Cancer Analysis. Lancet Oncol. 2017, 18, 1009–1021.
103. Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N. Engl. J. Med. 2015, 372, 2509–2520.
104. Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Mutational Landscape Determines Sensitivity to PD-1 Blockade in Non–Small Cell Lung Cancer. Science 2015, 348, 124–128.
105. Anagnostou, V.; Smith, K.N.; Forde, P.M.; Niknafs, N.; Bhattacharya, R.; White, J.; Zhang, T.; Adleff, V.; Phallen, J.; Wali, N.; et al. Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer. Cancer Discov. 2017, 7, 264–276.
106. McGrail, D.J.; Pilié, P.G.; Rashid, N.U.; Voorwerk, L.; Slagter, M.; Kok, M.; Jonasch, E.; Khasraw, M.; Heimberger, A.B.; Lim, B.; et al. High Tumor Mutation Burden Fails to Predict Immune Checkpoint Blockade Response across All Cancer Types. Ann. Oncol. 2021, 32, 661–672.
107. Wu, J.; Mayer, A.T.; Li, R. Integrated Imaging and Molecular Analysis to Decipher Tumor Microenvironment in the Era of Immunotherapy. Semin Cancer Biol. 2020, S1044–579X(20)30264–9.
108. Wu, J.; Li, C.; Gensheimer, M.; Padda, S.; Kato, F.; Shirato, H.; Wei, Y.; Schönlieb, C.-B.; Price, S.J.; Jaffray, D.; et al. Radiological Tumour Classification across Imaging Modality and Histology. Nat. Mach. Intell. 2021, 3, 787–798.
109. Kalaora, S.; Lee, J.S.; Barnea, E.; Levy, R.; Greenberg, P.; Alon, M.; Yagel, G.; Bar Eli, G.; Oren, R.; Peri, A.; et al. Immunoproteasome Expression Is Associated with Better Prognosis and Response to Checkpoint Therapies in Melanoma. Nat. Commun. 2020, 11, 896.
110. Hugo, W.; Zaretsky, J.M.; Sun, L.; Song, C.; Moreno, B.H.; Hu-Lieskovan, S.; Berent-Maoz, B.; Pang, J.; Chmielowski, B.; Cherry, G.; et al. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell 2016, 165, 35–44.
111. Neubert, N.J.; Tillé, L.; Barras, D.; Soneson, C.; Baumgaertner, P.; Rimoldi, D.; Gfeller, D.; Delorenzi, M.; Fuertes Marraco, S.A.; Speiser, D.E. Broad and Conserved Immune Regulation by Genetically Heterogeneous Melanoma Cells. Cancer Res. 2017, 77, 1623–1636.
112. Rodig, S.J.; Gusenleitner, D.; Jackson, D.G.; Gjini, E.; Giobbie-Hurder, A.; Jin, C.; Chang, H.; Lovitch, S.B.; Horak, C.; Weber, J.S.; et al. MHC Proteins Confer Differential Sensitivity to CTLA-4 and PD-1 Blockade in Untreated Metastatic Melanoma. Sci. Transl. Med. 2018, 10, eaar3342.
113. Grasso, C.S.; Tsoi, J.; Onyshchenko, M.; Abril-Rodriguez, G.; Ross-Macdonald, P.; Wind-Rotolo, M.; Champhekar, A.; Medina, E.; Torrejon, D.Y.; Shin, D.S.; et al. Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma. Cancer Cell 2020, 38, 500–515.e3.
114. Karachaliou, N.; Gonzalez-Cao, M.; Crespo, G.; Drozdowskyj, A.; Aldeguer, E.; Gimenez-Capitan, A.; Teixido, C.; Molina-Vila, M.A.; Viteri, S.; Gil, M.d.; et al. Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients. Ther. Adv. Med. Oncol. 2018, 18.
115. Ribas, A.; Medina, T.; Kummar, S.; Amin, A.; Kalbasi, A.; Drabick, J.J.; Barve, M.; Daniels, G.A.; Wong, D.J.; Schmidt, E.V.; et al. SD-101 in Combination with Pembrolizumab in Advanced Melanoma: Results of a Phase Ib, Multicenter Study. Cancer Discov. 2018, 8, 1250–1257.
116. Torrejon, D.Y.; Abril-Rodriguez, G.; Champhekar, A.S.; Tsoi, J.; Campbell, K.M.; Kalbasi, A.; Parisi, G.; Zaretsky, J.M.; Garcia-Diaz, A.; Puig-Saus, C.; et al. Overcoming Genetically Based Resistance Mechanisms to PD-1 Blockade. Cancer Discov. 2020, 10, 1140–1157.
117. Woods, K.; Knights, A.J.; Anaka, M.; Schittenhelm, R.B.; Purcell, A.W.; Behren, A.; Cebon, J. Mismatch in Epitope Specificities between IFNγ Inflamed and Uninflamed Conditions Leads to Escape from T Lymphocyte Killing in Melanoma. J. Immunother. Cancer 2016, 4, 10.
118. Peng, W.; Lizée, G.; Hwu, P. Blockade of the PD-1 Pathway Enhances the Efficacy of Adoptive Cell Therapy against Cancer. Onco. Immunol. 2013, 2, e22691.
119. Carvalho, A.S.; Rodríguez, M.S.; Matthiesen, R. Review and Literature Mining on Proteostasis Factors and Cancer. Methods Mol. Biol. 2016, 1449, 71–84.
120. Vahid, S.; Thaper, D.; Zoubeidi, A. Chaperoning the Cancer: The Proteostatic Functions of the Heat Shock Proteins in Cancer. Recent Pat. Anticancer Drug Discov. 2017, 12, 35–47.
121. Santoro, A.M.; D’Urso, A.; Cunsolo, A.; Milardi, D.; Purrello, R.; Sbardella, D.; Tundo, G.R.; Diana, D.; Fattorusso, R.; Dato, A.D.; et al. Cooperative Binding of the Cationic Porphyrin Tris-T4 Enhances Catalytic Activity of 20S Proteasome Unveiling a Complex Distribution of Functional States. Int. J. Mol. Sci. 2020, 21, 7190.
122. Santoro, A.M.; Cunsolo, A.; D’Urso, A.; Sbardella, D.; Tundo, G.R.; Ciaccio, C.; Coletta, M.; Diana, D.; Fattorusso, R.; Persico, M.; et al. Cationic Porphyrins Are Tunable Gatekeepers of the 20S Proteasome. Chem. Sci. 2016, 7, 1286–1297.
123. Dato, A.D.; Cunsolo, A.; Persico, M.; Santoro, A.M.; D’Urso, A.; Milardi, D.; Purrello, R.; Stefanelli, M.; Paolesse, R.; Tundo, G.R.; et al. Electrostatic Map Of Proteasome α-Rings Encodes The Design of Allosteric Porphyrin-Based Inhibitors Able To Affect 20S Conformation By Cooperative Binding. Sci. Rep. 2017, 7, 17098.
124. Goldberg, A.L.; Kim, H.T.; Lee, D.; Collins, G.A. Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation. Biomolecules 2021, 11, 779.
125. Kudriaeva, A.A.; Saratov, G.A.; Kaminskaya, A.N.; Vladimirov, V.I.; Barzilovich, P.Y.; Belogurov, A.A. Polyamines Counteract Carbonate-Driven Proteasome Stalling in Alkaline Conditions. Biomolecules 2020, 10, 1597.
126. Cotton, A.D.; Nguyen, D.P.; Gramespacher, J.A.; Seiple, I.A.; Wells, J.A. Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1. J. Am. Chem. Soc. 2021, 143, 593–598.
127. Wang, Y.; Deng, S.; Xu, J. Proteasomal and Lysosomal Degradation for Specific and Durable Suppression of Immunotherapeutic Targets. Cancer Biol. Med. 2020, 17, 583–598.
128. Hu, X.; Wang, J.; Chu, M.; Liu, Y.; Wang, Z.; Zhu, X. Emerging Role of Ubiquitination in the Regulation of PD-1/PD-L1 in Cancer Immunotherapy. Mol. Ther. 2021, 29, 908–919.