Akhmetzyanova I, Zelinskyy G, Littwitz-Salomon E, Malyshkina A, Dietze KK, Streeck H, et al. CD137 Agonist Therapy Can Reprogram Regulatory T Cells into cytotoxic CD4 + T cells with Antitumor Activity. J Immunol (Baltimore Md: 1950). 2016;196(1):484–92. https://doi.org/10.4049/jimmunol.1403039.

Article  CAS  Google Scholar 

Aksoylar H-I, Boussiotis VA. PD-1 + Treg cells: a foe in cancer immunotherapy? Nat Immunol. 2020;21(11):1311–2. https://doi.org/10.1038/s41590-020-0801-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. https://doi.org/10.1056/NEJMoa0912217.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Atif M, Cherai M, Miyara M. Phenotypic and functional studies of human Treg cell subpopulations. Methods Mol Biology (Clifton N J). 2023;2559:153–69. https://doi.org/10.1007/978-1-0716-2647-4_11.

Article  CAS  Google Scholar 

Badoual Cécile, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay NEH, et al. Prognostic Value of Tumor-infiltrating CD4 + T-Cell subpopulations in Head and Neck cancers. Clin Cancer Res. 2006;12(2):465–72. https://doi.org/10.1158/1078-0432.CCR-05-1886.

Article  CAS  PubMed  Google Scholar 

Badoual Cécile, Hans S, Merillon N, Ryswick CV, Ravel P, Benhamouda N, et al. PD-1–Expressing tumor-infiltrating T cells are a favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer. Cancer Res. 2013;73(1):128–38. https://doi.org/10.1158/0008-5472.CAN-12-2606.

Article  CAS  PubMed  Google Scholar 

Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, 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 (London England). 2019;394(10212):1915–28. https://doi.org/10.1016/S0140-6736(19)32591-7.

Article  CAS  PubMed  Google Scholar 

Castellsagué X, Alemany L, Quer M, Halec G, Quirós B, Tous S, et al. HPV involvement in Head and Neck cancers: Comprehensive Assessment of biomarkers in 3680 patients. J Natl Cancer Inst. 2016;108(6):djv403. https://doi.org/10.1093/jnci/djv403.

Article  CAS  PubMed  Google Scholar 

Chen S, Lee L-F, Fisher TS, Jessen B, Elliott M, Evering W, et al. Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model. Cancer Immunol Res. 2015;3(2):149–60. https://doi.org/10.1158/2326-6066.CIR-14-0118.

Article  CAS  PubMed  Google Scholar 

Chu D-T, Bac ND, Nguyen K-H, Tien NLB, Thanh VV, Nga VT, et al. An update on Anti-CD137 antibodies in Immunotherapies for Cancer. Int J Mol Sci. 2019;20(8). https://doi.org/10.3390/ijms20081822.

Cioni B, Jordanova ES, Hooijberg E, van der Linden R, de Menezes RX, Tan K, et al. HLA class II expression on tumor cells and low numbers of tumor-associated macrophages predict clinical outcome in oropharyngeal cancer. Head Neck. 2019;41(2):463–78. https://doi.org/10.1002/hed.25442.

Article  PubMed  Google Scholar 

Curran MA, Geiger TL, Montalvo W, Kim M, Reiner SL, Al-Shamkhani A, et al. Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin. J Exp Med. 2013;210(4):743–55. https://doi.org/10.1084/jem.20121190.

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Vos von Steenwijk PJ, Heusinkveld M, Ramwadhdoebe TH, Löwik MJ, van der Hulst JM, Goedemans R, et al. An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancer. Cancer Res. 2010;70(7):2707–17. https://doi.org/10.1158/0008-5472.CAN-09-4299

Dhume K, Kaye B, McKinstry KK. Regulation of CD4 T cell responses by the transcription factor eomesodermin. Biomolecules. 2022;12(11):1549. https://doi.org/10.3390/biom12111549.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dixon ML, Luo L, Ghosh S, Grimes JM, Leavenworth JD, Leavenworth JW. Remodeling of the tumor microenvironment via disrupting Blimp1 + effector Treg activity augments response to anti-PD-1 blockade. Mol Cancer. 2021;20(1):150. https://doi.org/10.1186/s12943-021-01450-3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dubrot J, Milheiro F, Alfaro C, Palazón A, Martinez-Forero I, Perez-Gracia JL, et al. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol Immunotherapy: CII. 2010;59(8):1223–33. https://doi.org/10.1007/s00262-010-0846-9.

Article  CAS  PubMed  Google Scholar 

Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang S-C, et al. Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun. 2021;12(1):1047. https://doi.org/10.1038/s41467-021-21383-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Geuijen C, Tacken P, Wang L-C, Klooster R, van Loo PF, Zhou J, et al. A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade. Nat Commun. 2021;12(1):4445. https://doi.org/10.1038/s41467-021-24767-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Glynn JP, McCoy JL, Fefer A. Cross-resistance to the transplantation of syngeneic friend, Moloney, and Rauscher virus-induced tumors. Cancer Res. 1968;28:434–9.

CAS  PubMed  Google Scholar 

Goodwin RG, Din WS, Davis-Smith T, Anderson DM, Gimpel SD, Sato TA, et al. Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor. Eur J Immunol. 1993;23(10):2631–41. https://doi.org/10.1002/eji.1830231037.

Article  CAS  PubMed  Google Scholar 

Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, et al. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J Clin Investig. 2014;124(5):2246–59. https://doi.org/10.1172/JCI73639.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.

Article  CAS  PubMed  Google Scholar 

Hewavisenti R, Ferguson A, Wang K, Jones D, Gebhardt T, Edwards J, et al. CD103 + tumor-resident CD8 + T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma. J Immunother Cancer. 2020;8(1):e000452. https://doi.org/10.1136/jitc-2019-000452.

Article  PubMed  PubMed Central  Google Scholar 

Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Sci (New York N Y). 2003;299(5609):1057–61. https://doi.org/10.1126/science.1079490.

Article  CAS  Google Scholar 

Houot R, Kohrt H. CD137 stimulation enhances the vaccinal effect of anti-tumor antibodies. Oncoimmunology. 2014;3(7):e941740. https://doi.org/10.4161/21624011.2014.941740.

Article  PubMed  PubMed Central  Google Scholar 

Hu B-S, Tang T, Jia J-L, Xie B-C, Wu T-L, Sheng Y-Y, et al. CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8 + T cells via NF-κB signaling. Cancer Cell Int. 2020;20:513. https://doi.org/10.1186/s12935-020-01605-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hur JY, Ku BM, Park S, Jung HA, Lee SH, Ahn MJ. Prognostic value of FOXP3 + regulatory T cells for patients with locally advanced oropharyngeal squamous cell carcinoma. PLoS ONE. 2022;17(10):e0274830. https://doi.org/10.1371/journal.pone.0274830.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Joshi K, de Massy MR, Ismail M, Reading JL, Uddin I, Woolston A, et al. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat Med. 2019;25(10):1549–59. https://doi.org/10.1038/s41591-019-0592-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kang SW, Lee SC, Park SH, Kim J, Kim HH, Lee H-W, et al. Anti-CD137 suppresses Tumor Growth by blocking Reverse Signaling by CD137 Ligand. Cancer Res. 2017;77(21):5989–6000. https://doi.org/10.1158/0008-5472.CAN-17-0610.

Article  CAS  PubMed  Google Scholar 

Kang Y-K, Reck M, Nghiem P, Feng Y, Plautz G, Kim HR, et al. Assessment of hyperprogression versus the natural course of disease development with nivolumab with or without ipilimumab versus placebo in phase III, randomized, controlled trials. J Immunother Cancer. 2022;10(4):e004273. https://doi.org/10.1136/jitc-2021-004273.

Article  PubMed  PubMed Central  Google Scholar 

Karaki S, Blanc C, Tran T, Galy-Fauroux I, Mougel A, Dransart E, et al. CXCR6 deficiency impairs cancer vaccine efficacy and CD8 + resident memory T-cell recruitment in head and neck and lung tumors. J Immunother Cancer. 2021;9(3):e001948. https://doi.org/10.1136/jitc-2020-001948.

Article  PubMed  PubMed Central  Google Scholar 

Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, et al. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. J Immunother Cancer. 2021;9(4):e001955. https://doi.org/10.1136/jitc-2020-001955.

Article  PubMed  PubMed Central  Google Scholar 

Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakamura H, Takeuchi Y, et al. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol. 2020;21(11):1346–58. https://doi.org/10.1038/s41590-020-0769