REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
2. Estimated number of new cases from 2020 to 2040, Incidence, Both sexes, age [0-85+]. Africa + Latin America and Caribbean + Northern America + Europe + Oceania + Asia. Available from: https://gco.iarc.fr/tomorrow/en/dataviz/tables?mode=cancer&group_populations=1. [Last accessed on 29 May 2023].
4. Osazuwa-Peters N, Simpson MC, Zhao L, et al. Suicide risk among cancer survivors: Head and neck versus other cancers. Cancer 2018;124:4072-9.
5. Giralt J, Benavente S, Arguis M. Optimizing approaches to head and neck cancer: strengths and weaknesses in multidisciplinary treatments of locally advanced disease. Ann Oncol 2008;19 Suppl 7:vii195-9.
6. Machiels J-P, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31:1462-75.
7. Orlandi E, Iacovelli NA, Tombolini V, et al. Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer. Oral Oncol 2019;99:104453.
8. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. NEJM 2010;363:24-35.
9. Golusiński W. Functional organ preservation surgery in head and neck cancer: transoral robotic surgery and beyond. Front Oncol 2019;9:293.
10. Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol 2009;27:3684-90.
11. Nichols AC, Theurer J, Prisman E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol 2019;20:1349-59.
12. Nenclares P, Rullan A, Tam K, Dunn LA, St John M, Harrington KJ. Introducing checkpoint inhibitors into the curative setting of head and neck cancers: lessons learned, future considerations. Am Soc Clin Oncol Educ Book 2022;42:1-16.
13. Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856-67.
14. Cohen EEW, Soulières D, Le Tourneau C, et al. KEYNOTE-040 investigators. 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;393:156-67.
15. Burtness B, Harrington KJ, Greil R, et al. KEYNOTE-048 Investigators. 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;394:1915-28.
16. Riaz N, Sherman E, Pei X, et al. Precision radiotherapy: reduction in radiation for oropharyngeal cancer in the 30 ROC trial. J Natl Cancer Inst 2021;113:742-51.
17. Kimple RJ, Smith MA, Blitzer GC, et al. Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res 2013;73:4791-800.
18. Hill RM, Rocha S, Parsons JL. Overcoming the impact of hypoxia in driving radiotherapy resistance in head and neck squamous cell carcinoma. Cancers 2022;14:4130.
19. Menegakis A, Klompmaker R, Vennin C, et al. Resistance of hypoxic cells to ionizing radiation is mediated in part via hypoxia-induced quiescence. Cells 2021;10:610.
20. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 2020;6:92.
21. D’Cruz AK, Vaish R, Kapre N, et al. Head and neck disease management group. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 2015;373:521-9.
22. Koyfman SA, Ismaila N, Crook D, et al. Management of the neck in squamous cell carcinoma of the oral cavity and oropharynx: ASCO clinical practice guideline. J Clin Oncol 2019;37:1753-74.
23. Sher DJ, Pham NL, Shah JL, et al. Prospective phase 2 study of radiation therapy dose and volume de-escalation for elective neck treatment of oropharyngeal and laryngeal cancer. Int J Radiat Oncol Biol Phys 2021;109:932-40.
24. Deschuymer S, Nevens D, Duprez F, et al. Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome. Radiother Oncol 2020;143:24-9.
25. Marciscano AE, Ghasemzadeh A, Nirschl TR, et al. Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy. Clin Cancer Res 2018;24:5058-71.
26. Lund AW. Immune Potential Untapped: Leveraging the Lymphatic System for Cancer Immunotherapy. Cancer Immunol Res 2022;10:1042-6.
27. Bois H, Heim TA, Lund AW. Tumor-draining lymph nodes: at the crossroads of metastasis and immunity. Sci Immunol 2021;6:eabg3551.
28. Pereira ER, Kedrin D, Seano G, et al. Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science 2018;359:1403-7.
29. Ruffin AT, Li H, Vujanovic L, Zandberg DP, Ferris RL, Bruno TC. Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment. Nat Rev Cancer 2023;23:173-88.
30. Saddawi-Konefka R, Simon AB, Sumner W, Sharabi A, Mell LK, Cohen EEW. Defining the role of immunotherapy in the curative treatment of locoregionally advanced head and neck cancer: promises, challenges, and opportunities. Front Oncol 2021;11:738626.
31. Kim HAJ, Zeng PYF, Shaikh MH, et al. All HPV-negative head and neck cancers are not the same: Analysis of the TCGA dataset reveals that anatomical sites have distinct mutation, transcriptome, hypoxia, and tumor microenvironment profiles. Oral Oncol 2021;116:105260.
32. Bhandari V, Hoey C, Liu LY, et al. Molecular landmarks of tumor hypoxia across cancer types. Nat Genet 2019;51:308-18.
33. Van den Bossche V, Zaryouh H, Vara-Messler M, et al. Microenvironment-driven intratumoral heterogeneity in head and neck cancers: clinical challenges and opportunities for precision medicine. Drug Resist Updat 2022;60:100806.
34. Folaron M, Merzianu M, Duvvuri U, Ferris RL, Seshadri M. Profiling the stromal and vascular heterogeneity in patient-derived xenograft models of head and neck cancer: impact on therapeutic response. Cancers 2019;11:951.
35. Cai MC, Zhao X, Cao M, et al. T-cell exhaustion interrelates with immune cytolytic activity to shape the inflamed tumor microenvironment. J Pathol 2020;251:147-59.
36. Beltra JC, Manne S, Abdel-Hakeem MS, et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 2020;52:825-841.e8.
37. Zhao X, Shan Q, Xue HH. TCF1 in T cell immunity: a broadened frontier. Nat Rev Immunol 2022;22:147-57.
38. Zehn D, Thimme R, Lugli E, de Almeida GP, Oxenius A. ‘Stem-like’ precursors are the fount to sustain persistent CD8+ T cell responses. Nat Immunol 2022;23:836-47.
39. Zhang Z, Chen L, Chen H, et al. Pan-cancer landscape of T-cell exhaustion heterogeneity within the tumor microenvironment revealed a progressive roadmap of hierarchical dysfunction associated with prognosis and therapeutic efficacy. EBioMedicine 2022;83:104207.
40. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013;31:563-604.
41. Zagorulya M, Duong E, Spranger S. Impact of anatomic site on antigen-presenting cells in cancer. J Immunother Cancer 2020;8:e001204.
42. Darragh LB, Karam SD. Amateur antigen-presenting cells in the tumor microenvironment. Mol Carcinog 2022;61:153-64.
43. Seliger B, Kloor M, Ferrone S. HLA class II antigen-processing pathway in tumors: molecular defects and clinical relevance. Oncoimmunology 2017;6:e1171447.
44. Näsman A, Andersson E, Marklund L, et al. HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome. PLoS One 2013;8:e77025.
45. Thiery J. Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions. Explor Target Antitumor Ther 2022;3:598-629.
46. Puram SV, Tirosh I, Parikh AS, et al. Single-Cell Transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 2017;171:1611-1624.e24.
47. Obradovic A, Graves D, Korrer M, et al. Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer. Clin Cancer Res 2022;28:2094-109.
48. André P, Denis C, Soulas C, et al. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell 2018;175:1731-1743.e13.
49. Salomé B, Sfakianos JP, Ranti D, et al. NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer. Cancer Cell 2022;40:1027-1043.e9.
50. van Montfoort N, Borst L, Korrer MJ, et al. NKG2A blockade potentiates CD8 T cell immunity induced by cancer vaccines. Cell 2018;175:1744-1755.e15.
51. Battaglia NG, Murphy JD, Uccello TP, et al. Combination of NKG2A and PD-1 blockade improves radiotherapy response in radioresistant tumors. J Immunol 2022;209:629-40.
52. Chandler C, Liu T, Buckanovich R, Coffman LG. The double edge sword of fibrosis in cancer. Transl Res 2019;209:55-67.
53. Dufrusine B, Damiani V, Capone E, et al. BAG3 induces fibroblasts to release key cytokines involved in pancreatic cell migration. J Cell Biochem 2022;123:65-76.
54. Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov 2019;18:99-115.
56. De Marco M, Del Papa N, Reppucci F, et al. BAG3 induces α-SMA expression in human fibroblasts and its over-expression correlates with poorer survival in fibrotic cancer patients. J Cell Biochem 2022;123:91-101.
57. Bronte V, Brandau S, Chen SH, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 2016;7:12150.
58. Bailey CM, Liu Y, Liu M, et al. Targeting HIF-1α abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues. J Clin Invest 2022:132.
59. Tumino N, Besi F, Martini S, et al. Polymorphonuclear myeloid-derived suppressor cells are abundant in peripheral blood of cancer patients and suppress natural killer cell anti-tumor activity. Front Immunol 2021;12:803014.
60. Choi J, Suh B, Ahn YO, et al. CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function. Tumour Biol 2012;33:121-9.
61. Zhou X, Fang D, Liu H, et al. PMN-MDSCs accumulation induced by CXCL1 promotes CD8+ T cells exhaustion in gastric cancer. Cancer Lett 2022;532:215598.
62. Tsai MS, Chen WC, Lu CH, Chen MF. The prognosis of head and neck squamous cell carcinoma related to immunosuppressive tumor microenvironment regulated by IL-6 signaling. Oral Oncol 2019;91:47-55.
63. Sridharan V, Margalit DN, Lynch SA, et al. Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer. Br J Cancer 2016;115:252-60.
64. Telarovic I, Wenger RH, Pruschy M. Interfering with Tumor Hypoxia for Radiotherapy Optimization. J Exp Clin Cancer Res 2021;40:197.
65. Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 2014;211:781-90.
66. Ohl K, Tenbrock K. Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol 2018;9:2499.
67. Sprouse ML, Welte T, Boral D, et al. PMN-MDSCs enhance CTC metastatic properties through reciprocal interactions via ROS/Notch/Nodal signaling. Int J Mol Sci 2019;20:1916.
68. Jiménez-Cortegana C, Galassi C, Klapp V, Gabrilovich DI, Galluzzi L. Myeloid-derived suppressor cells and radiotherapy. Cancer Immunol Res 2022;10:545-57.
69. Muroyama Y, Nirschl TR, Kochel CM, et al. Stereotactic radiotherapy increases functionally suppressive regulatory t cells in the tumor microenvironment. Cancer Immunol Res 2017;5:992-1004.
70. Boustani J, Joseph ELM, Martin E, et al. Cisplatin-based chemoradiation decreases telomerase-specific CD4 TH1 response but increases immune suppressive cells in peripheral blood. BMC Immunol 2021;22:38.
71. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015;520:373-7.
72. Oweida AJ, Darragh L, Phan A, et al. STAT3 modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst 2019;111:1339-49.
73. Oweida A, Hararah MK, Phan A, et al. Resistance to radiotherapy and PD-L1 blockade is mediated by TIM-3 upregulation and regulatory T-Cell infiltration. Clin Cancer Res 2018;24:5368-80.
74. Knitz MW, Bickett TE, Darragh LB, et al. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. J Immunother Cancer 2021;9:e001955.
75. Akhmetzyanova I, Zelinskyy G, Littwitz-Salomon E, et al. CD137 agonist therapy can reprogram regulatory T cells into cytotoxic CD4+ T cells with antitumor activity. J Immunol 2016;196:484-92.
76. Kondoh N, Mizuno-Kamiya M. The role of immune modulatory cytokines in the tumor microenvironments of head and neck squamous cell carcinomas. Cancers 2022;14:2884.
77. Karakasheva TA, Lin EW, Tang Q, et al. IL-6 mediates cross-talk between tumor cells and activated fibroblasts in the tumor microenvironment. Cancer Res 2018;78:4957-70.
78. Dar AA, Patil RS, Pradhan TN, Chaukar DA, D'Cruz AK, Chiplunkar SV. Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma. Cancer Immunol Immunother 2020;69:1071-86.
79. Koucký V, Hladíková K, Táborská E, et al. The cytokine milieu compromises functional capacity of tumor-infiltrating plasmacytoid dendritic cells in HPV-negative but not in HPV-positive HNSCC. Cancer Immunol Immunother 2021;70:2545-57.
80. Sotirović J, Perić A, Vojvodić D, et al. Serum cytokine profile of laryngeal squamous cell carcinoma patients. J Laryngol Otol 2017;131:455-61.
81. Batlle E, Massagué J. Transforming growth factor-β signaling in immunity and cancer. Immunity 2019;50:924-40.
82. Strait AA, Woolaver RA, Hall SC, et al. Distinct immune microenvironment profiles of therapeutic responders emerge in combined TGFβ/PD-L1 blockade-treated squamous cell carcinoma. Commun Biol 2021;4:1005.
83. Redman JM, Friedman J, Robbins Y, et al. Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck cancer. J Clin Invest 2022:132.
84. Drouillard D, Craig BT, Dwinell MB. Physiology of chemokines in the cancer microenvironment. Am J Physiol Cell Physiol 2023;324:C167-82.
86. Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science 2017:355.
87. William WN Jr, Zhao X, Bianchi JJ, et al. Immune evasion in HPV- head and neck precancer-cancer transition is driven by an aneuploid switch involving chromosome 9p loss. Proc Natl Acad Sci U S A 2021:118.
88. Han G, Yang G, Hao D, et al. 9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy. Nat Commun 2021;12:5606.
89. Zhao X, Cohen EEW, William WN Jr, et al. Somatic 9p24.1 alterations in HPV- head and neck squamous cancer dictate immune microenvironment and anti-PD-1 checkpoint inhibitor activity. Proc Natl Acad Sci U S A 2022;119:e2213835119.
90. Litchfield K, Reading JL, Puttick C, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021;184:596-614.e14.
91. Read GH, Bailleul J, Vlashi E, Kesarwala AH. Metabolic response to radiation therapy in cancer. Mol Carcinog 2022;61:200-24.
92. Lewis JE, Kemp ML. Integration of machine learning and genome-scale metabolic modeling identifies multi-omics biomarkers for radiation resistance. Nat Commun 2021;12:2700.
94. Mittal A, Nenwani M, Sarangi I, Achreja A, Lawrence TS, Nagrath D. Radiotherapy-induced metabolic hallmarks in the tumor microenvironment. Trends Cancer 2022;8:855-69.
95. Vaupel P, Schmidberger H, Mayer A. The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol 2019;95:912-9.
96. Pavlova NN, Zhu J, Thompson CB. The hallmarks of cancer metabolism: Still emerging. Cell Metab 2022;34:355-77.
97. Yan SX, Luo XM, Zhou SH, et al. Effect of antisense oligodeoxynucleotides glucose transporter-1 on enhancement of radiosensitivity of laryngeal carcinoma. Int J Med Sci 2013;10:1375-86.
98. Mims J, Bansal N, Bharadwaj MS, et al. Energy metabolism in a matched model of radiation resistance for head and neck squamous cell cancer. Radiat Res 2015;183:291-304.
99. Jung YS, Najy AJ, Huang W, et al. HPV-associated differential regulation of tumor metabolism in oropharyngeal head and neck cancer. Oncotarget 2017;8:51530-41.
100. Matsuoka Y, Yoshida R, Kawahara K, et al. The antioxidative stress regulator Nrf2 potentiates radioresistance of oral squamous cell carcinoma accompanied with metabolic modulation. Lab Invest 2022;102:896-907.
101. Leu M, Kitz J, Pilavakis Y, et al. Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome. Sci Rep 2021;11:4578.
102. Rabinowitz JD, Enerbäck S. Lactate: the ugly duckling of energy metabolism. Nat Metab 2020;2:566-71.
103. Gao Y, Zhou H, Liu G, Wu J, Yuan Y, Shang A. Tumor microenvironment: lactic acid promotes tumor development. J Immunol Res 2022;2022:3119375.
104. Apostolova P, Pearce EL. Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment. Trends Immunol 2022;43:969-77.
105. Kaymak I, Luda KM, Duimstra LR, et al. Carbon source availability drives nutrient utilization in CD8+ T cells. Cell Metab 2022;34:1298-1311.e6.
106. Feng Q, Liu Z, Yu X, et al. Lactate increases stemness of CD8+T cells to augment anti-tumor immunity. Nat Commun 2022;13:4981.
107. Choi JE, Sebastian C, Ferrer CM, et al. A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma. Nat Metab 2021;3:182-95.
108. Tang Y, Zhang Z, Chen Y, et al. Metabolic adaptation-mediated cancer survival and progression in oxidative stress. Antioxidants 2022;11:1324.
109. Sitthideatphaiboon P, Galan-Cobo A, Negrao MV, et al. STK11/LKB1 mutations in NSCLC are associated with KEAP1/NRF2-dependent radiotherapy resistance targetable by glutaminase inhibition. Clin Cancer Res 2021;27:1720-33.
110. Claiborne MD, Leone R. Differential glutamine metabolism in the tumor microenvironment - studies in diversity and heterogeneity: a mini-review. Front Oncol 2022;12:1011191.
111. Best SA, Gubser PM, Sethumadhavan S, et al. Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer. Cell Metab 2022;34:874-887.e6.
112. Lang X, Green MD, Wang W, et al. Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11. Cancer Discov 2019;9:1673-85.
113. Lee J, Roh JL. Ferroptosis induction via targeting metabolic alterations in head and neck cancer. Crit Rev Oncol Hematol 2023;181:103887.
114. Wang L, Zhao X, Fu J, Xu W, Yuan J. The role of tumour metabolism in cisplatin resistance. Front Mol Biosci 2021;8:691795.
115. Moretton A, Loizou JI. Interplay between cellular metabolism and the DNA damage response in cancer. Cancers 2020;12:2051.
116. Ludwig N, Gillespie DG, Reichert TE, Jackson EK, Whiteside TL. Purine metabolites in tumor-derived exosomes may facilitate immune escape of head and neck squamous cell carcinoma. Cancers 2020;12:1602.
117. Jiang Z, Hsu JL, Li Y, Hortobagyi GN, Hung MC. Cancer Cell Metabolism Bolsters Immunotherapy Resistance by Promoting an Immunosuppressive Tumor Microenvironment. Front Oncol 2020;10:1197.
118. Yegutkin GG, Boison D. ATP and adenosine metabolism in cancer: exploitation for therapeutic gain. Pharmacol Rev 2022;74:797-822.
119. Ma SR, Deng WW, Liu JF, et al. Blockade of adenosine A2A receptor enhances CD8+ T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma. Mol Cancer 2017;16:99.
120. Deng WW, Li YC, Ma SR, et al. Specific blockade CD73 alters the “exhausted” phenotype of T cells in head and neck squamous cell carcinoma. Int J Cancer 2018;143:1494-504.
121. Darragh LB, Oweida AJ, Karam SD. Overcoming resistance to combination radiation-immunotherapy: a focus on contributing pathways within the tumor microenvironment. Front Immunol 2018;9:3154.
122. Augustin RC, Leone RD, Naing A, Fong L, Bao R, Luke JJ. Next steps for clinical translation of adenosine pathway inhibition in cancer immunotherapy. J Immunother Cancer 2022;10:e004089.
124. O’Sullivan D, van der Windt GJW, Huang SC, et al. Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity 2018;49:375-6.
125. Pascual G, Avgustinova A, Mejetta S, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 2017;541:41-5.
126. Corbet C, Bastien E, Santiago de Jesus JP, et al. TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun 2020;11:454.
127. Lei G, Zhang Y, Koppula P, et al. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression. Cell Res 2020;30:146-62.
128. Pearson AN, Carmicheal J, Jiang L, Lei YL, Green MD. Contribution of lipid oxidation and ferroptosis to radiotherapy efficacy. Int J Mol Sci 2021;22:12603.
129. Roh JL, Kim EH, Jang H, Shin D. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol 2017;11:254-62.
130. Okazaki S, Umene K, Yamasaki J, et al. Glutaminolysis-related genes determine sensitivity to xCT-targeted therapy in head and neck squamous cell carcinoma. Cancer Sci 2019;110:3453-63.
131. Kim R, Hashimoto A, Markosyan N, et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature 2022;612:338-46.
132. Taylor CT, Colgan SP. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol 2017;17:774-85.
133. Chung SW, Xie Y, Suk JS. Overcoming physical stromal barriers to cancer immunotherapy. Drug Deliv Transl Res 2021;11:2430-47.
134. Lee P, Chandel NS, Simon MC. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol 2020;21:268-83.
135. Godet I, Shin YJ, Ju JA, Ye IC, Wang G, Gilkes DM. Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat Commun 2019;10:4862.
136. Butturini E, Carcereri de Prati A, Boriero D, Mariotto S. Tumor dormancy and interplay with hypoxic tumor microenvironment. Int J Mol Sci 2019;20:4305.
137. Rühle A, Grosu AL, Wiedenmann N, et al. Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with head-and-neck squamous cell carcinoma undergoing chemoradiation. Theranostics 2020;10:9395-406.
138. Nicolay NH, Rühle A, Wiedenmann N, et al. Lymphocyte Infiltration Determines the Hypoxia-Dependent Response to Definitive Chemoradiation in Head-and-Neck Cancer: Results from a Prospective Imaging Trial. J Nucl Med 2021;62:471-8.
139. Notarbartolo S, Abrignani S. Human T lymphocytes at tumor sites. Semin Immunopathol 2022;44:883-901.
140. Zagorulya M, Spranger S. Once upon a prime: DCs shape cancer immunity. Trends Cancer 2023;9:172-84.
141. Saddawi-Konefka R, O'Farrell A, Faraji F, et al. Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC. Nat Commun 2022;13:4298.
142. Engelmann L, Thierauf J, Koerich Laureano N, et al. Organotypic Co-cultures as a novel 3D model for head and neck squamous cell carcinoma. Cancers 2020;12:2330.
143. Lugo-Cintrón KM, Ayuso JM, Humayun M, et al. Primary head and neck tumour-derived fibroblasts promote lymphangiogenesis in a lymphatic organotypic co-culture model. EBioMedicine 2021;73:103634.
144. Miserocchi G, Cocchi C, De Vita A, et al. Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas. Cancer Biol Med 2021;18:502-16.
145. Mattei F, Andreone S, Mencattini A, et al. Oncoimmunology meets organs-on-chip. Front Mol Biosci 2021;8:627454.
146. Sontheimer-Phelps A, Hassell BA, Ingber DE. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer 2019;19:65-81.
147. Riaz N, Havel JJ, Makarov V, et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 2017;171:934-949.e16.
148. Stafford M, Kaczmar J. The neoadjuvant paradigm reinvigorated: a review of pre-surgical immunotherapy in HNSCC. Cancers Head Neck 2020;5:4.
149. Farlow JL, Birkeland AC, Swiecicki PL, Brenner JC, Spector ME. Window of opportunity trials in head and neck cancer. J Cancer Metastasis Treat 2019;5:18.
150. Darragh LB, Knitz MM, Hu J, et al. A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC. Nat Cancer 2022;3:1300-17.
151. Vaziri Fard E, Ali Y, Wang XI, et al. Tumor-infiltrating lymphocyte volume is a better predictor of disease-free survival than stromal tumor-infiltrating lymphocytes in invasive breast carcinoma. Am J Clin Pathol 2019;152:656-65.
152. Vos JL, Elbers JBW, Krijgsman O, et al. Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma. Nat Commun 2021;12:7348.
153. Lee CK, Jeong SH, Jang C, et al. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science 2019;363:644-9.
154. Li M, Xian HC, Tang YJ, Liang XH, Tang YL. Fatty acid oxidation: driver of lymph node metastasis. Cancer Cell Int 2021;21:339.
155. Gillot L, Baudin L, Rouaud L, Kridelka F, Noël A. The pre-metastatic niche in lymph nodes: formation and characteristics. Cell Mol Life Sci 2021;78:5987-6002.
156. Wong BW, Wang X, Zecchin A, et al. The role of fatty acid β-oxidation in lymphangiogenesis. Nature 2017;542:49-54.
157. Zhang Q, Wang H, Mao C, et al. Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol 2018;94:27-35.
158. Ma Q, Dieterich LC, Ikenberg K, et al. Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread. Sci Adv 2018;4:eaat4758.
159. Iwamoto H, Abe M, Yang Y, et al. Cancer lipid metabolism confers antiangiogenic drug resistance. Cell Metab 2018;28:104-117.e5.
160. Reticker-Flynn NE, Zhang W, Belk JA, et al. Lymph node colonization induces tumor-immune tolerance to promote distant metastasis. Cell 2022;185:1924-1942.e23.
161. Wang W, Green M, Choi JE, et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 2019;569:270-4.
162. Chen X, Kang R, Kroemer G, Tang D. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 2021;18:280-96.