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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賈景山(Jean-San Chia) | |
dc.contributor.author | Hsiang-Fong Kao | en |
dc.contributor.author | 高祥豐 | zh_TW |
dc.date.accessioned | 2023-03-19T23:24:30Z | - |
dc.date.copyright | 2022-04-26 | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022-04-15 | |
dc.identifier.citation | 1. Health Promotion Registration MoHaW, Taiwan: Cancer Registry Annual Report, 2011, Taiwan. 2014. 2. Hsu WL, Chien YC, Chiang CJ, Yang HI, Lou PJ, Wang CP, Yu KJ, You SL, Wang LY, Chen SY et al: Lifetime risk of distinct upper aerodigestive tract cancers and consumption of alcohol, betel and cigarette. Int J Cancer 2014, 135(6):1480-1486. 3. Argiris A, Karamouzis MV, Raben D, Ferris RL: Head and neck cancer. The Lancet 2008, 371(9625):1695-1709. 4. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M et al: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004, 350(19):1937-1944. 5. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M et al: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004, 350(19):1945-1952. 6. Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Syddall H, Sayer AA, Cooper C, Lord JM: The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell 2012, 11(5):912-915. 7. Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ et al: Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007, 357(17):1705-1715. 8. Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH et al: Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007, 357(17):1695-1704. 9. Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, Tan M, Fasciano J, Sammartino DE, Posner MR et al: Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol 2011, 12(2):153-159. 10. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008, 359(11):1116-1127. 11. Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, Jarrett C, Carter J, Murphy BA, Netterville J et al: Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 2006, 24(25):4170-4176. 12. Temam S, Kawaguchi H, El-Naggar AK, Jelinek J, Tang H, Liu DD, Lang W, Issa JP, Lee JJ, Mao L: Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J Clin Oncol 2007, 25(16):2164-2170. 13. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J et al: Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010, 11(1):21-28. 14. Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-674. 15. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010, 363(8):711-723. 16. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD: Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol 2015, 33(17):1889-1894. 17. Ferris RL, Blumenschein G, Jr., Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C et al: Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016, 375(19):1856-1867. 18. Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R et al: Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019, 393(10167):156-167. 19. Syn NL, Teng MWL, Mok TSK, Soo RA: De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol 2017, 18(12):e731-e741. 20. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC et al: Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 2018, 24(5):541-550. 21. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V et al: PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014, 515(7528):568-571. 22. Duan Q, Zhang H, Zheng J, Zhang L: Turning Cold into Hot: Firing up the Tumor Microenvironment. Trends Cancer 2020, 6(7):605-618. 23. Nishikawa H, Sakaguchi S: Regulatory T cells in tumor immunity. Int J Cancer 2010, 127(4):759-767. 24. Pan Y, Yu Y, Wang X, Zhang T: Tumor-Associated Macrophages in Tumor Immunity. Front Immunol 2020, 11:583084. 25. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D: Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 2020, 20(1):7-24. 26. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA: Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 2015, 12(5):453-457. 27. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD et al: The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 2015, 21(8):938-945. 28. Engblom C, Pfirschke C, Pittet MJ: The role of myeloid cells in cancer therapies. Nat Rev Cancer 2016, 16(7):447-462. 29. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS et al: Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014, 371(23):2189-2199. 30. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D et al: PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015, 372(26):2509-2520. 31. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS et al: Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015, 348(6230):124-128. 32. Venkatesan S, Angelova M, Puttick C, Zhai H, Caswell DR, Lu WT, Dietzen M, Galanos P, Evangelou K, Bellelli R et al: Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution. Cancer Discov 2021, 11(10):2456-2473. 33. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L et al: Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. New England Journal of Medicine 2016, 375(9):819-829. 34. Gattinoni L, Ji Y, Restifo NP: Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy. Clin Cancer Res 2010, 16(19):4695-4701. 35. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L et al: Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015, 372(21):2018-2028. 36. Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH et al: Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol 2016, 34(32):3838-3845. 37. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, Fell HP, Ferree S, George RD, Grogan T et al: Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 2008, 26(3):317-325. 38. Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P et al: Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013, 31(11):1023-1031. 39. Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP: Systems biology. Conditional density-based analysis of T cell signaling in single-cell data. Science 2014, 346(6213):1250689. 40. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES et al: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005, 102(43):15545-15550. 41. Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G, Jr., Psyrri A, Baste N, Neupane P, Bratland A et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 2019, 394(10212):1915-1928. 42. Kalbasi A, Ribas A: Tumour-intrinsic resistance to immune checkpoint blockade. Nat Rev Immunol 2020, 20(1):25-39. 43. Chen DS, Mellman I: Oncology meets immunology: the cancer-immunity cycle. Immunity 2013, 39(1):1-10. 44. Jansen CS, Prokhnevska N, Master VA, Sanda MG, Carlisle JW, Bilen MA, Cardenas M, Wilkinson S, Lake R, Sowalsky AG et al: An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature 2019, 576(7787):465-470. 45. Basham TY, Merigan TC: Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol 1983, 130(4):1492-1494. 46. Lee JH, Shklovskaya E, Lim SY, Carlino MS, Menzies AM, Stewart A, Pedersen B, Irvine M, Alavi S, Yang JYH et al: Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition. Nat Commun 2020, 11(1):1897. 47. Concha-Benavente F, Srivastava RM, Trivedi S, Lei Y, Chandran U, Seethala RR, Freeman GJ, Ferris RL: Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNgamma That Induce PD-L1 Expression in Head and Neck Cancer. Cancer Res 2016, 76(5):1031-1043. 48. Leibowitz MS, Srivastava RM, Andrade Filho PA, Egloff AM, Wang L, Seethala RR, Ferrone S, Ferris RL: SHP2 is overexpressed and inhibits pSTAT1-mediated APM component expression, T-cell attracting chemokine secretion, and CTL recognition in head and neck cancer cells. Clin Cancer Res 2013, 19(4):798-808. 49. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G: Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell 2015, 28(6):690-714. 50. Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF et al: Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2018, 378(22):2078-2092. 51. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A et al: First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 2021, 398(10294):27-40. 52. Lizotte PH, Hong RL, Luster TA, Cavanaugh ME, Taus LJ, Wang S, Dhaneshwar A, Mayman N, Yang A, Kulkarni M et al: A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing. Cancer Immunol Res 2018, 6(12):1511-1523. 53. Guo Y, Ahn MJ, Chan A, Wang CH, Kang JH, Kim SB, Bello M, Arora RS, Zhang Q, He X et al: Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial. Ann Oncol 2019, 30(11):1831-1839. 54. Machiels J-PH, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ et al: Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. The Lancet Oncology 2015, 16(5):583-594. 55. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003, 13(11):2498-2504. 56. Merico D, Isserlin R, Stueker O, Emili A, Bader GD: Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 2010, 5(11):e13984. 57. Doncheva NT, Morris JH, Gorodkin J, Jensen LJ: Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data. J Proteome Res 2019, 18(2):623-632. 58. Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V et al: Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. Cell 2018, 173(2):291-304 e296. 59. Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulieres D, Le Tourneau C, Licitra L, Burtness B et al: Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol 2021, 34(3):532-541. 60. Litchfield K, Reading JL, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins TBK, Rosenthal R, Biswas D, Rowan A et al: Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021, 184(3):596-614 e514. 61. House IG, Savas P, Lai J, Chen AXY, Oliver AJ, Teo ZL, Todd KL, Henderson MA, Giuffrida L, Petley EV et al: Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade. Clin Cancer Res 2020, 26(2):487-504. 62. Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD et al: A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med 2018, 24(8):1178-1191. 63. Lee JJ, Kao KC, Chiu YL, Jung CJ, Liu CJ, Cheng SJ, Chang YL, Ko JY, Chia JS: Enrichment of Human CCR6(+) Regulatory T Cells with Superior Suppressive Activity in Oral Cancer. J Immunol 2017, 199(2):467-476. 64. Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ et al: CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature 2019, 572(7769):392-396. 65. Mowen KA, Tang J, Zhu W, Schurter BT, Shuai K, Herschman HR, David M: Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription. Cell 2001, 104(5):731-741. 66. Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, Chen T, Roszik J, Bernatchez C, Woodman SE et al: Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. Cell 2016, 167(2):397-404 e399. 67. Sacco AG, Chen R, Worden FP, Wong DJL, Adkins D, Swiecicki P, Chai-Ho W, Oppelt P, Ghosh D, Bykowski J et al: Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol 2021, 22(6):883-892. 68. Taylor MH, Lee CH, Makker V, Rasco D, Dutcus CE, Wu J, Stepan DE, Shumaker RC, Motzer RJ: Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J Clin Oncol 2020, 38(11):1154-1163. 69. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R et al: Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med 2019, 381(16):1535-1546. 70. Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S et al: Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018, 378(14):1277-1290. 71. Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E et al: Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2019, 381(21):2020-2031. 72. Ferris RL, Haddad R, Even C, Tahara M, Dvorkin M, Ciuleanu TE, Clement PM, Mesia R, Kutukova S, Zholudeva L et al: Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann Oncol 2020, 31(7):942-950. 73. Argiris A, Harrington K, Tahara M, Ferris RL, Gillison M, Fayette J, Daste A, Koralewski P, Mesia Nin R, Saba NF et al: LBA36 Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651. Ann Oncol 2021, 32:S1310-S1311. 74. Harrington KJ, Kong A, Mach N, Chesney JA, Fernandez BC, Rischin D, Cohen EEW, Radcliffe HS, Gumuscu B, Cheng J et al: Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clin Cancer Res 2020, 26(19):5153-5161. 75. Massarelli E, William W, Johnson F, Kies M, Ferrarotto R, Guo M, Feng L, Lee JJ, Tran H, Kim YU et al: Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial. JAMA Oncol 2019, 5(1):67-73. 76. Rodriguez CP, Wu QV, Voutsinas J, Fromm JR, Jiang X, Pillarisetty VG, Lee SM, Santana-Davila R, Goulart B, Baik CS et al: A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent Metastatic Head and Neck Squamous Cell Carcinomas and Salivary Gland Cancer. Clin Cancer Res 2020, 26(4):837-845. 77. Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P et al: Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Clin Cancer Res 2020, 26(19):5140-5152. 78. Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, Sher X, Liu XQ, Lu H, Nebozhyn M et al: Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 2018, 362(6411). 79. Tu HF, Ko CJ, Lee CT, Lee CF, Lan SW, Lin HH, Lin HY, Ku CC, Lee DY, Chen IC et al: Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD. Cancer Res 2021, 81(12):3270-3282. 80. Yang JC, Gadgeel SM, Sequist LV, Wu CL, Papadimitrakopoulou VA, Su WC, Fiore J, Saraf S, Raftopoulos H, Patnaik A: Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation. J Thorac Oncol 2019, 14(3):553-559. 81. Yang JC, Shepherd FA, Kim DW, Lee GW, Lee JS, Chang GC, Lee SS, Wei YF, Lee YG, Laus G et al: Osimertinib Plus Durvalumab versus Osimertinib Monotherapy in EGFR T790M-Positive NSCLC following Previous EGFR TKI Therapy: CAURAL Brief Report. J Thorac Oncol 2019, 14(5):933-939. 82. Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR: Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol 2017, 28(10):2377-2385. 83. Gohil SH, Iorgulescu JB, Braun DA, Keskin DB, Livak KJ: Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat Rev Clin Oncol 2021, 18(4):244-256. 84. Lundberg E, Borner GHH: Spatial proteomics: a powerful discovery tool for cell biology. Nat Rev Mol Cell Biol 2019, 20(5):285-302. 85. Ignatiadis M, Sledge GW, Jeffrey SS: Liquid biopsy enters the clinic - implementation issues and future challenges. Nat Rev Clin Oncol 2021, 18(5):297-312. 86. The Cancer Genome Atlas N, Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, Getz G, Ally A, Balasundaram M et al: Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015, 517:576. 87. Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR et al: CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov 2018, 8(2):216-233. 88. Schaer DA, Beckmann RP, Dempsey JA, Huber L, Forest A, Amaladas N, Li Y, Wang YC, Rasmussen ER, Chin D et al: The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade. Cell reports 2018, 22(11):2978-2994. 89. Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ, Melms JC, Leeson R, Kanodia A, Mei S, Lin JR et al: A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade. Cell 2018, 175(4):984-997 e924. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85791 | - |
dc.description.abstract | 腫瘤微環境(tumor microenvironment)的調控被認為可增加計畫性死亡蛋白-受體1抗體(anti-programmed cell death protein 1 antibody, or anti PD-1 antibody)的治療效果。在細胞與動物試驗中發現,抑制表皮生長因子受體(epithelial growth factor receptor, EGFR)可誘發腫瘤呈現抗原,並增強anti-PD-1的效果。本研究計畫假設,藉由合併使用EGFR酪胺酸激酶抑制劑(tyrosine kinase inhibitor) afatinib以及pembrolizumab 免疫調節點抑制劑,可增進免疫治療於頭頸癌的成效。本研究的臨床試驗(NCT03695510),完成29位病患的收案與治療。整體腫瘤達客觀縮小的比例為 41.4%。於檢體研究中發現,在治療後,腫瘤微環境內之抗原表現及免疫活化之相關基因組的表現有顯著上升。在腫瘤基因突變分析中,我們發現未改變的methylthioadenosine phosphorylase (unaltered MTAP)者的檢體有較偏向炎性反應的腫瘤微環境,有較佳的治療反應及治療預後。我們利用cytometry by time-of-flight (CyTOF)分析chemokine receptor,可以觀察到不同的異質性存在於各類型細胞中。本研究藉由臨床試驗,證實afatinib-pembrolizumab對於頭頸癌病患的治療成效。腫瘤微環境的研究證實此治療可增加微環境內的抗原表現。同時找到MTAP為可能的預後因子。接下來我們將繼續發展其他可能的人體免疫學多面向生物資訊學分析模式,建立頭頸癌免疫癌症治療轉譯醫學研究模式。 | zh_TW |
dc.description.abstract | Tumor microenvironment (TME) modulation may improve programmed cell death 1 (PD-1)-targeted antibody therapy efficacy. Epidermal growth factor receptor (EGFR) pathway inhibition upregulates tumor antigen presentation machinery within the TME in preclinical models. We hypothesized that the irreversible EGFR tyrosine kinase inhibitor afatinib combined with pembrolizumab (anti–PD-1) would improve outcomes in head and neck squamous cell carcinoma (HNSCC) patients. A Phase II trial (NCT03695510) including 29 eligible patients met its primary endpoint by improving the objective partial response (objective response rate, 41.4%). The post-treatment, paired-tissue analysis revealed afatinib plus pembrolizumab upregulated antigen presentation machinery and increased inflammation in TME. Tumors with unaltered methyl-thioadenosine phosphorylase (MTAP) had an inflamed TME and predicted better clinical benefits. Proteomics analysis of PD-1+ T cells using cytometry by time-of-flight (CyTOF) identified the chemokine receptor landscape. In conclusion, afatinib augments pembrolizumab therapy and improves the ORR in HNSCC patients by upregulating antigen presentation machinery in TME. Unaltered MTAP may predict a favorable TME and serve as a predictive biomarker for anti–PD-1 therapy. | en |
dc.description.provenance | Made available in DSpace on 2023-03-19T23:24:30Z (GMT). No. of bitstreams: 1 U0001-1404202213353000.pdf: 4741872 bytes, checksum: f1c15d4b3736a8f59595b61c87e4bf24 (MD5) Previous issue date: 2022 | en |
dc.description.tableofcontents | 口試委員會審訂書 i Acknowledgement ii 中文摘要 iii Abstract iv Contents v List of Tables ix List of Figures ix Chapter 1 Introduction 1 1.1 Head and neck squamous cell carcinoma in Taiwan 1 1.2 Treatment for recurrent or metastatic HNSCC in the pre- immunotherapy era 2 1.3 Immune checkpoint inhibitors for HNSCC 3 1.4 Tumor microenvironment and genomics 4 1.4.1 Immune cells in the tumor microenvironment 4 1.4.2 Cancer genomics and the tumor microenvironment 6 1.4.3 Lessons from research in the tumor microenvironment: Finding biomarkers 7 1.4.4 Bioinformatics and multi-omics approaches to human immunology 8 1.5 Anti–PD-1 combination therapy in HNSCC: Rationale and current landscape 10 1.5.1 Overcoming intrinsic resistance in anti–PD-1 therapy 10 1.5.2 The role of the antigen presentation machinery in anti–PD-1 therapies 11 1.5.3 Anti–PD-1 therapy combined with chemotherapy: Current landscapes and unmet needs 11 1.6 The role of the EGFR signaling pathway in HNSCC immunotherapy 12 Chapter 2 Hypothesis and specific aims 14 2.1 Hypothesis 14 2.2 Specific aims 14 Chapter 3 Materials and methods 15 3.1 Clinical trials 15 3.1.1 Study approval 15 3.1.2 Study design 15 3.1.3 Efficacy assessment 16 3.1.4 mRNA expression analysis 17 3.1.5 Comprehensive genomic profiling 18 3.1.6 TCGA HNSCC data acquisition and analysis 19 3.1.7 PD-L1 testing 19 3.1.8 Statistical analysis 20 3.2 Deciphering the tumor microenvironment in HNSCC 21 3.2.1 Patient population and specimen collection 21 3.2.2 Isolation of peripheral blood mononuclear cells and T cells 22 3.2.3 Isolation of tumor-infiltrating lymphocytes 23 3.2.4 FACS staining and analysis 23 3.2.5 Flow cytometry using mass cytometry 24 Chapter 4 Results 26 4.1 Clinical studies 26 4.1.1 Afatinib plus pembrolizumab therapy showed improved efficacy in HNSCC patients 26 4.1.2 The toxicities associated with afatinib plus pembrolizumab therapy were tolerable 27 4.1.3 Biomarker analysis 27 4.1.3.1 mRNA expression analysis in paired biopsy tissues showed that afatinib plus pembrolizumab treatment augments antigen presentation machinery 27 4.1.3.2 Targeted gene sequencing analysis revealed that unaltered methyl-thioadenosine phosphorylase could serve as a potential biomarker for response to therapy 29 4.1.3.3 GSEA analysis using study data and TCGA data showed that tumors with unaltered MTAP presented an inflamed microenvironment 30 4.1.3.4 Post-progression, targeted gene sequence analysis revealed acquired loss of MTAP in a patient with disease progression after initial response 31 4.1.3.5 A high response rate is observed in patients with high PD-L1 expression 32 4.2 Microenvironment study using a multiplexed proteomics approach 32 4.2.1 Pilot experiment using CyTOF and trouble-shooting 32 4.2.2 CyTOF study using cancer patient tissues 36 4.2.2.1 Differences in CD3+ T cells between PBMCs and TILs 36 Chapter 5 Discussion 38 - Afatinib plus pembrolizumab therapy is an effective option for patients with HNSCC 38 - Multi-omics analysis of paired tissue samples revealed the upregulation of antigen presentation machinery and the stimulation of immune functions in the tumor microenvironment 38 - Genetics studies and post-progression biopsies revealed that unaltered MTAP may regulate immune functions in the tumor microenvironment 40 - The outlook for anti–PD-1 combination therapy in HNSCC 41 - Next steps: extend the DoR achieved for afatinib plus pembrolizumab combination therapy 42 - Mechanisms of acquired resistance to afatinib plus pembrolizumab combination therapy: what do we know? 43 - Toxicities associated with afatinib plus pembrolizumab therapy in HNSCC 45 - Limitations of this prospective study 46 - A journey in CyTOF study: lessons learned 48 - Conclusion 49 Chapter 6 Future works 50 6.1 Real-world analysis of anti–PD-1 therapy in patients with HNSCC and accompanying biomarker analysis 50 6.2 Ribociclib, an anti-CDK4/6 inhibitor, combined with anti–PD-1 for HNSCC treatment 50 6.3 Personalized anti–PD-1 combination therapy in patients with HNSCC 52 Chapter 7 Tables 53 Chapter 8 Figures 56 Chapter 9 Reference 85 Chapter 10 Appendix 94 10.1 Journal papers related with this dissertation 94 10.2 Open data of the study 94 | |
dc.language.iso | en | |
dc.title | 以生物資訊學模式探討腫瘤微環境對頭頸癌病患接受免疫調節點抑制劑複方治療之效應研究 | zh_TW |
dc.title | Bioinformatic approach to tumor microenvironment in head and neck squamous cell carcinoma patients taking immune checkpoint inhibitor combination therapy | en |
dc.type | Thesis | |
dc.date.schoolyear | 110-2 | |
dc.description.degree | 博士 | |
dc.contributor.author-orcid | 0000-0001-9186-0134 | |
dc.contributor.coadvisor | 洪瑞隆(Ruey-Long Hong) | |
dc.contributor.oralexamcommittee | 林進清(Jin-Ching Lin),楊慕華(Muh-Hwa Yang),江伯倫(Bor-Luen Chiang),許秉寧(Ping-Ning Hsu),顧家綺(Chia-Chi Ku) | |
dc.subject.keyword | 頭頸癌,癌症免疫治療,腫瘤微環境,生物資訊學,afatinib,pembrolizumab, | zh_TW |
dc.subject.keyword | head and neck squamous cell carcinoma,cancer immunotherapy,tumor microenvironment,bioinformatics,afatinib,pembrolizumab, | en |
dc.relation.page | 94 | |
dc.identifier.doi | 10.6342/NTU202200697 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2022-04-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
dc.date.embargo-lift | 2022-04-26 | - |
顯示於系所單位: | 免疫學研究所 |
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