Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primer. 2020;6:92.

Article  Google Scholar 

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.

Article  CAS  PubMed  Google Scholar 

Cohen MH, Chen H, Shord S, Fuchs C, He K, Zhao H, et al. Approval summary: cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Oncologist. 2013;18:460–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993;328:184–94.

Article  CAS  PubMed  Google Scholar 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, 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.

Article  PubMed  Google Scholar 

Chen D, Wu M, Li Y, Chang I, Yuan Q, Ekimyan-Salvo M, et al. Targeting BMI1+ cancer stem cells overcomes chemoresistance and inhibits metastases in squamous cell carcinoma. Cell Stem Cell. 2017;20:621-634.e6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marin-Acevedo JA, Chirila RM, Dronca RS. immune checkpoint inhibitor toxicities. Mayo Clin Proc. 2019;94:1321–9.

Article  CAS  PubMed  Google Scholar 

Abdel-Wahab N, Shah M, Lopez-Olivo MA, Suarez-Almazor ME. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern Med. 2018;168:121–30.

Article  PubMed  Google Scholar 

DuMontier C, Loh KP, Bain PA, Silliman RA, Hshieh T, Abel GA, et al. Defining undertreatment and overtreatment in older adults with cancer: a scoping literature review. J Clin Oncol Off J Am Soc Clin Oncol. 2020;38:2558–69.

Article  Google Scholar 

Zhang K, Zhang L, Mi Y, Tang Y, Ren F, Liu B, et al. A ceRNA network and a potential regulatory axis in gastric cancer with different degrees of immune cell infiltration. Cancer Sci. 2020;111:4041–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schirrmacher V. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int J Oncol. 2019;54:407–19.

Article  CAS  PubMed  Google Scholar 

Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68.

Article  CAS  PubMed  Google Scholar 

Ling DC, Bakkenist CJ, Ferris RL, Clump DA. Role of Immunotherapy in Head and Neck Cancer. Semin Radiat Oncol. 2018;28:12–6.

Article  PubMed  Google Scholar 

Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay RE, Luoma AM, et al. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science. 2018;359:770–5.

Danaher P, Warren S, Dennis L, D’Amico L, White A, Disis ML, et al. Gene expression markers of Tumor Infiltrating Leukocytes. J Immunother Cancer. 2017;5:18.

Article  PubMed  PubMed Central  Google Scholar 

Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neo SY, Lundqvist A. The Multifaceted Roles of CXCL9 Within the Tumor Microenvironment. Adv Exp Med Biol. 2020;1231:45–51.

Article  CAS  PubMed  Google Scholar 

Tian Y, Wen C, Zhang Z, Liu Y, Li F, Zhao Q, et al. CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy. Cancer Immunol Immunother CII. 2022;71:2663–75.

Article  CAS  PubMed  Google Scholar 

Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation—a target for novel cancer therapy. Cancer Treat Rev. 2018;63:40–7.

Article  CAS  PubMed  Google Scholar 

Hsin L-J, Kao H-K, Chen I-H, Tsang N-M, Hsu C-L, Liu S-C, et al. Serum CXCL9 levels are associated with tumor progression and treatment outcome in patients with nasopharyngeal carcinoma. PLoS ONE. 2013;8: e80052.

Article  PubMed  PubMed Central  Google Scholar 

Wild CA, Brandau S, Lindemann M, Lotfi R, Hoffmann TK, Lang S, et al. Toll-like receptors in regulatory t cells of patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2010;136:1253–9.

Article  PubMed  Google Scholar 

Wu Z-H, Niu X, Wu G-H, Cheng Q. Decreased expression of TNFRSF12A in thyroid gland cancer predicts poor prognosis: a study based on TCGA data. Medicine (Baltimore). 2020;99: e21882.

Article  CAS  PubMed  Google Scholar 

Chen G, Sun J, Xie M, Yu S, Tang Q, Chen L. PLAU promotes cell proliferation and epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Front Genet. 2021;12: 651882.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xia L, Jiang L, Chen Y, Zhang G, Chen L. ThPOK transcriptionally inactivates TNFRSF12A to increase the proliferation of T cells with the involvement of the NF-kB pathway. Cytokine. 2021;148: 155658.

Article  CAS  PubMed  Google Scholar 

Yao Y, Yan Z, Lian S, Wei L, Zhou C, Feng D, et al. Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma. J Immunother Cancer. 2020;8: e000444.

Article  PubMed  PubMed Central  Google Scholar 

Budhwani M, Turrell G, Yu M, Frazer IH, Mehdi AM, Chandra J. Immune-inhibitory gene expression is positively correlated with overall immune activity and predicts increased survival probability of cervical and head and neck cancer patients. Front Mol Biosci. 2021;8: 622643.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li MO, Flavell RA. TGF-beta: a master of all T cell trades. Cell. 2008;134:392–404.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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

Article  PubMed  PubMed Central  Google Scholar 

Jie H-B, Gildener-Leapman N, Li J, Srivastava RM, Gibson SP, Whiteside TL, et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 2013;109:2629–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Speiser DE, Lee SY, Wong B, Arron J, Santana A, Kong YY, et al. A regulatory role for TRAF1 in antigen-induced apoptosis of T cells. J Exp Med. 1997;185:1777–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Oh H, Grinberg-Bleyer Y, Liao W, Maloney D, Wang P, Wu Z, et al. An NF-κB transcription-factor-dependent lineage-specific transcriptional program promotes regulatory T cell identity and function. Immunity. 2017;47:450-465.e5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yixing C, Xie F, Chen J, Dayu L, Li Z, Luo Q, et al. The LMP1/Lgals1-NF-Kb-IRF1-PDL1 axis promotes immune escape in nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2022;114: e514.

Article  Google Scholar 

Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019;18:10.

Article  PubMed  PubMed Central  Google Scholar 

Gameiro SF, Ghasemi F, Barrett JW, Koropatnick J, Nichols AC, Mymryk JS, et al. Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy. Oncoimmunology. 2018;7: e1498439.

Article  PubMed  PubMed Central  Google Scholar 

Kumar D. Regulation of glycolysis in head and neck squamous cell carcinoma. Postdoc J J Postdr Res Postdr Aff. 2017;5:14–28.

Google Scholar 

Li X, Wenes M, Romero P, Huang SC-C, Fendt S-M, Ho P-C. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 2019;16:425–41.

Article  CAS  PubMed  Google Scholar 

Dom