Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma

Mandal, R.; Şenbabaoğlu, Y.; Desrichard, A.; Havel, J.J.; Dalin, M.G.; Riaz, N.; Lee, K.W.; Ganly, I.; Hakimi, A.A.; Chan, T.A.; Morris, L.G.T. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight, 2016, 1(17), e89829.
[http://dx.doi.org/10.1172/jci.insight.89829] [PMID: 27777979]

Chi, A.C.; Day, T.A.; Neville, B.W. Oral cavity and oropharyngeal squamous cell carcinoma—an update. CA Cancer J. Clin., 2015, 65(5), 401-421.
[http://dx.doi.org/10.3322/caac.21293] [PMID: 26215712]

Johnson, D.E.; Burtness, B.; Leemans, C.R.; Lui, V.W.Y.; Bauman, J.E.; Grandis, J.R. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Primers, 2020, 6(1), 92.
[http://dx.doi.org/10.1038/s41572-020-00224-3] [PMID: 33243986]

Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]

Burtness, B.; Harrington, K.J.; Greil, R.; Soulières, D.; Tahara, M.; de Castro, G., Jr; Psyrri, A.; Basté, N.; Neupane, P.; Bratland, Å.; Fuereder, T.; Hughes, B.G.M.; Mesía, R.; Ngamphaiboon, N.; Rordorf, T.; Wan Ishak, W.Z.; Hong, R.L.; González Mendoza, R.; Roy, A.; Zhang, Y.; Gumuscu, B.; Cheng, J.D.; Jin, F.; Rischin, D.; Lerzo, G.; Tatangelo, M.; Varela, M.; Zarba, J.J.; Boyer, M.; Gan, H.; Gao, B.; Hughes, B.; Mallesara, G.; Rischin, D.; Taylor, A.; Burian, M.; Fuereder, T.; Greil, R.; Barrios, C.H.; de Castro Junior, D.O.; Castro, G.; Franke, F.A.; Girotto, G.; Lima, I.P.F.; Nicolau, U.R.; Pinto, G.D.J.; Santos, L.; Victorino, A-P.; Chua, N.; Couture, F.; Gregg, R.; Hansen, A.; Hilton, J.; McCarthy, J.; Soulieres, D.; Ascui, R.; Gonzalez, P.; Villanueva, L.; Torregroza, M.; Zambrano, A.; Holeckova, P.; Kral, Z.; Melichar, B.; Prausova, J.; Vosmik, M.; Andersen, M.; Gyldenkerne, N.; Jurgens, H.; Putnik, K.; Reinikainen, P.; Gruenwald, V.; Laban, S.; Aravantinos, G.; Boukovinas, I.; Georgoulias, V.; Psyrri, A.; Kwong, D.; Al-Farhat, Y.; Csoszi, T.; Erfan, J.; Horvai, G.; Landherr, L.; Remenar, E.; Ruzsa, A.; Szota, J.; Billan, S.; Gluck, I.; Gutfeld, O.; Popovtzer, A.; Benasso, M.; Bui, S.; Ferrari, V.; Licitra, L.; Nole, F.; Fujii, T.; Fujimoto, Y.; Hanai, N.; Hara, H.; Matsumoto, K.; Mitsugi, K.; Monden, N.; Nakayama, M.; Okami, K.; Oridate, N.; Shiga, K.; Shimizu, Y.; Sugasawa, M.; Tahara, M.; Takahashi, M.; Takahashi, S.; Tanaka, K.; Ueda, T.; Yamaguchi, H.; Yamazaki, T.; Yasumatsu, R.; Yokota, T.; Yoshizaki, T.; Kudaba, I.; Stara, Z.; Wan Ishak, W.Z.; Cheah, S.K.; Aguilar Ponce, J.; Gonzalez Mendoza, R.; Hernandez Hernandez, C.; Medina Soto, F.; Buter, J.; Hoeben, A.; Oosting, S.; Suijkerbuijk, K.; Bratland, A.; Brydoey, M.; Alvarez, R.; Mas, L.; Caguioa, P.; Querol, J.; Regala, E.E.; Tamayo, M.B.; Villegas, E.M.; Kawecki, A.; Karpenko, A.; Klochikhin, A.; Smolin, A.; Zarubenkov, O.; Goh, B.C.; Cohen, G.; du Toit, J.; Jordaan, C.; Landers, G.; Ruff, P.; Szpak, W.; Tabane, N.; Brana, I.; Iglesias Docampo, L.; Lavernia, J.; Mesia, R.; Abel, E.; Muratidu, V.; Nielsen, N.; Cristina, V.; Rordorf, T.; Rothschild, S.; Hong, R-L.; Wang, H-M.; Yang, M-H.; Yeh, S-P.; Yen, C-J.; Ngamphaiboon, N.; Soparattanapaisarn, N.; Sriuranpong, V.; Aksoy, S.; Cicin, I.; Ekenel, M.; Harputluoglu, H.; Ozyilkan, O.; Harrington, K.; Agarwala, S.; Ali, H.; Alter, R.; Anderson, D.; Bruce, J.; Burtness, B.; Campbell, N.; Conde, M.; Deeken, J.; Edenfield, W.; Feldman, L.; Gaughan, E.; Goueli, B.; Halmos, B.; Hegde, U.; Hunis, B.; Jotte, R.; Karnad, A.; Khan, S.; Laudi, N.; Laux, D.; Martincic, D.; McCune, S.; McGaughey, D.; Misiukiewicz, K.; Mulford, D.; Nadler, E.; Neupane, P.; Nunnink, J.; Ohr, J.; O’Malley, M.; Patson, B.; Paul, D.; Popa, E.; Powell, S.; Redman, R.; Rella, V.; Rocha Lima, C.; Sivapiragasam, A.; Su, Y.; Sukari, A.; Wong, S.; Yilmaz, E.; Yorio, J. 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.
[http://dx.doi.org/10.1016/S0140-6736(19)32591-7] [PMID: 31679945]

Gomes-da-Silva, L.C.; Kepp, O.; Kroemer, G. Regulatory approval of photoimmunotherapy: Photodynamic therapy that induces immunogenic cell death. OncoImmunology, 2020, 9(1), 1841393.
[http://dx.doi.org/10.1080/2162402X.2020.1841393] [PMID: 33178498]

Amaria, R.N.; Prieto, P.A.; Tetzlaff, M.T.; Reuben, A.; Andrews, M.C.; Ross, M.I.; Glitza, I.C.; Cormier, J.; Hwu, W.J.; Tawbi, H.A.; Patel, S.P.; Lee, J.E.; Gershenwald, J.E.; Spencer, C.N.; Gopalakrishnan, V.; Bassett, R.; Simpson, L.; Mouton, R.; Hudgens, C.W.; Zhao, L.; Zhu, H.; Cooper, Z.A.; Wani, K.; Lazar, A.; Hwu, P.; Diab, A.; Wong, M.K.; McQuade, J.L.; Royal, R.; Lucci, A.; Burton, E.M.; Reddy, S.; Sharma, P.; Allison, J.; Futreal, P.A.; Woodman, S.E.; Davies, M.A.; Wargo, J.A. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: A single-centre, open-label, randomised, phase 2 trial. Lancet Oncol., 2018, 19(2), 181-193.
[http://dx.doi.org/10.1016/S1470-2045(18)30015-9] [PMID: 29361468]

Wusiman, D.; Li, W.; Guo, L.; Huang, Z.; Zhang, Y.; Zhang, X.; Zhao, X.; Li, L.; An, Z.; Li, Z.; Ying, J.; An, C. Comprehensive analysis of single-cell and bulk RNA-sequencing data identifies B cell marker genes signature that predicts prognosis and analysis of immune checkpoints expression in head and neck squamous cell carcinoma. Heliyon, 2023, 9(12), e22656.
[http://dx.doi.org/10.1016/j.heliyon.2023.e22656] [PMID: 38125461]

Wu, X.; Gu, Z.; Chen, Y.; Chen, B.; Chen, W.; Weng, L.; Liu, X. Application of PD-1 blockade in cancer immunotherapy. Comput. Struct. Biotechnol. J., 2019, 17, 661-674.
[http://dx.doi.org/10.1016/j.csbj.2019.03.006] [PMID: 31205619]

Gavrielatou, N.; Fortis, E.; Spathis, A.; Anastasiou, M.; Economopoulou, P.; Foukas, G.R.P.; Lelegiannis, I.M.; Rusakiewicz, S.; Vathiotis, I.; Aung, T.N.; Tissot, S.; Kastrinou, A.; Kotsantis, I.; Vagia, E.M.; Panayiotides, I.; Rimm, D.L.; Coukos, G.; Homicsko, K.; Foukas, P.; Psyrri, A. B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma. Ann. Oncol., 2023, S0923-7534(23)05118-9.
[http://dx.doi.org/10.1016/j.annonc.2023.12.011] [PMID: 38159908]

Borel, C.; Jung, A.C.; Burgy, M. Immunotherapy breakthroughs in the treatment of recurrent or metastatic head and neck squamous cell carcinoma. Cancers, 2020, 12(9), 2691.
[http://dx.doi.org/10.3390/cancers12092691] [PMID: 32967162]

Ferris, R.L.; Blumenschein, G., Jr; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.; Kasper, S.; Vokes, E.E.; Even, C.; Worden, F.; Saba, N.F.; Iglesias Docampo, L.C.; Haddad, R.; Rordorf, T.; Kiyota, N.; Tahara, M.; Monga, M.; Lynch, M.; Geese, W.J.; Kopit, J.; Shaw, J.W.; Gillison, M.L. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl. J. Med., 2016, 375(19), 1856-1867.
[http://dx.doi.org/10.1056/NEJMoa1602252] [PMID: 27718784]

Seiwert, T.Y.; Burtness, B.; Mehra, R.; Weiss, J.; Berger, R.; Eder, J.P.; Heath, K.; McClanahan, T.; Lunceford, J.; Gause, C.; Cheng, J.D.; Chow, L.Q. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): An open-label, multicentre, phase 1b trial. Lancet Oncol., 2016, 17(7), 956-965.
[http://dx.doi.org/10.1016/S1470-2045(16)30066-3] [PMID: 27247226]

Ruffin, A.T.; Cillo, A.R.; Tabib, T.; Liu, A.; Onkar, S.; Kunning, S.R.; Lampenfeld, C.; Atiya, H.I.; Abecassis, I.; Kürten, C.H.L.; Qi, Z.; Soose, R.; Duvvuri, U.; Kim, S.; Oesterrich, S.; Lafyatis, R.; Coffman, L.G.; Ferris, R.L.; Vignali, D.A.A.; Bruno, T.C. B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma. Nat. Commun., 2021, 12(1), 3349.
[http://dx.doi.org/10.1038/s41467-021-23355-x] [PMID: 34099645]

Economopoulou, P.; Kotsantis, I.; Psyrri, A. B cells and their role in shaping the immune response in squamous cell carcinoma of the head and neck. Immunotherapy, 2021, 13(9), 723-726.
[http://dx.doi.org/10.2217/imt-2021-0070] [PMID: 33910385]

Cabrita, R.; Lauss, M.; Sanna, A.; Donia, M.; Skaarup Larsen, M.; Mitra, S.; Johansson, I.; Phung, B.; Harbst, K.; Vallon-Christersson, J.; van Schoiack, A.; Lövgren, K.; Warren, S.; Jirström, K.; Olsson, H.; Pietras, K.; Ingvar, C.; Isaksson, K.; Schadendorf, D.; Schmidt, H.; Bastholt, L.; Carneiro, A.; Wargo, J.A.; Svane, I.M.; Jönsson, G. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature, 2020, 577(7791), 561-565.
[http://dx.doi.org/10.1038/s41586-019-1914-8] [PMID: 31942071]

Helmink, B.A.; Reddy, S.M.; Gao, J.; Zhang, S.; Basar, R.; Thakur, R.; Yizhak, K.; Sade-Feldman, M.; Blando, J.; Han, G.; Gopalakrishnan, V.; Xi, Y.; Zhao, H.; Amaria, R.N.; Tawbi, H.A.; Cogdill, A.P.; Liu, W.; LeBleu, V.S.; Kugeratski, F.G.; Patel, S.; Davies, M.A.; Hwu, P.; Lee, J.E.; Gershenwald, J.E.; Lucci, A.; Arora, R.; Woodman, S.; Keung, E.Z.; Gaudreau, P.O.; Reuben, A.; Spencer, C.N.; Burton, E.M.; Haydu, L.E.; Lazar, A.J.; Zapassodi, R.; Hudgens, C.W.; Ledesma, D.A.; Ong, S.; Bailey, M.; Warren, S.; Rao, D.; Krijgsman, O.; Rozeman, E.A.; Peeper, D.; Blank, C.U.; Schumacher, T.N.; Butterfield, L.H.; Zelazowska, M.A.; McBride, K.M.; Kalluri, R.; Allison, J.; Petitprez, F.; Fridman, W.H.; Sautès-Fridman, C.; Hacohen, N.; Rezvani, K.; Sharma, P.; Tetzlaff, M.T.; Wang, L.; Wargo, J.A. B cells and tertiary lymphoid structures promote immunotherapy response. Nature, 2020, 577(7791), 549-555.
[http://dx.doi.org/10.1038/s41586-019-1922-8] [PMID: 31942075]

Wu, Z.; Zhou, J.; Xiao, Y.; Ming, J.; Zhou, J.; Dong, F.; Zhou, X.; Xu, Z.; Zhao, X.; Lei, P.; Huang, T. CD20⁺CD22⁺ADAM28⁺ B cells in tertiary lymphoid structures promote immunotherapy response. Front. Immunol., 2022, 13, 865596.
[http://dx.doi.org/10.3389/fimmu.2022.865596] [PMID: 35634306]

Petitprez, F.; de Reyniès, A.; Keung, E.Z.; Chen, T.W.W.; Sun, C.M.; Calderaro, J.; Jeng, Y.M.; Hsiao, L.P.; Lacroix, L.; Bougoüin, A.; Moreira, M.; Lacroix, G.; Natario, I.; Adam, J.; Lucchesi, C.; Laizet, Y.; Toulmonde, M.; Burgess, M.A.; Bolejack, V.; Reinke, D.; Wani, K.M.; Wang, W.L.; Lazar, A.J.; Roland, C.L.; Wargo, J.A.; Italiano, A.; Sautès-Fridman, C.; Tawbi, H.A.; Fridman, W.H. B cells are associated with survival and immunotherapy response in sarcoma. Nature, 2020, 577(7791), 556-560.
[http://dx.doi.org/10.1038/s41586-019-1906-8] [PMID: 31942077]

Dieu-Nosjean, M.C.; Giraldo, N.A.; Kaplon, H.; Germain, C.; Fridman, W.H.; Sautès-Fridman, C. Tertiary lymphoid structures, drivers of the anti‐tumor responses in human cancers. Immunol. Rev., 2016, 271(1), 260-275.
[http://dx.doi.org/10.1111/imr.12405] [PMID: 27088920]

Tertiary lymphoid structures validated as biomarker.. Cancer Discov., 2023, OF1
[http://dx.doi.org/10.1158/2159-8290.CD-NB2023-0090]

Wang, X.; Juncker-Jensen, A.; Huang, G.; Nagy, M.L.; Lu, X.; Cheng, L.; Lu, X. Spatial relationship of tertiary lymphoid structures and tumor‐associated neutrophils in bladder cancer and prognostic potential for anti‐PD‐L1 immunotherapy. Cancer Commun., 2023, cac2.12491.
[http://dx.doi.org/10.1002/cac2.12491] [PMID: 37864307]

Calderaro, J.; Petitprez, F.; Becht, E.; Laurent, A.; Hirsch, T.Z.; Rousseau, B.; Luciani, A.; Amaddeo, G.; Derman, J.; Charpy, C.; Zucman-Rossi, J.; Fridman, W.H.; Sautès-Fridman, C. Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma. J. Hepatol., 2019, 70(1), 58-65.
[http://dx.doi.org/10.1016/j.jhep.2018.09.003] [PMID: 30213589]

Zhou, L.; Xu, B.; Liu, Y.; Wang, Z. Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in muscle-invasive bladder cancer. OncoImmunology, 2021, 10(1), 1915574.
[http://dx.doi.org/10.1080/2162402X.2021.1915574] [PMID: 34104539]

Wood, O.; Woo, J.; Seumois, G.; Savelyeva, N.; McCann, K.J.; Singh, D.; Jones, T.; Peel, L.; Breen, M.S.; Ward, M.; Garrido Martin, E.; Sanchez-Elsner, T.; Thomas, G.; Vijayanand, P.; Woelk, C.H.; King, E.; Ottensmeier, C.; Consortium, S. Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors. Oncotarget, 2016, 7(35), 56781-56797.
[http://dx.doi.org/10.18632/oncotarget.10788] [PMID: 27462861]

Schinke, H.; Shi, E.; Lin, Z.; Quadt, T.; Kranz, G.; Zhou, J.; Wang, H.; Hess, J.; Heuer, S.; Belka, C.; Zitzelsberger, H.; Schumacher, U.; Genduso, S.; Riecken, K.; Gao, Y.; Wu, Z.; Reichel, C.A.; Walz, C.; Canis, M.; Unger, K.; Baumeister, P.; Pan, M.; Gires, O. A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer. Mol. Cancer, 2022, 21(1), 178.
[http://dx.doi.org/10.1186/s12943-022-01646-1] [PMID: 36076232]

Li, H.; Zhu, S.W.; Zhou, J.J.; Chen, D.R.; Liu, J.; Wu, Z.Z.; Wang, W.Y.; Zhang, M.J.; Sun, Z.J. Tertiary lymphoid structure raises survival and immunotherapy in HPV ⁻ HNSCC. J. Dent. Res., 2023, 102(6), 678-688.
[http://dx.doi.org/10.1177/00220345231151685] [PMID: 36883630]

Shen, A.; Ye, Y.; Chen, F.; Xu, Y.; Zhang, Z.; Zhao, Q.; Zeng, Z. Integrated multi-omics analysis identifies CD73 as a prognostic biomarker and immunotherapy response predictor in head and neck squamous cell carcinoma. Front. Immunol., 2022, 13, 969034.
[http://dx.doi.org/10.3389/fimmu.2022.969034] [PMID: 36466881]

Chen, Y.; Li, Z.Y.; Zhou, G.Q.; Sun, Y. An immune-related gene prognostic index for head and neck squamous cell carcinoma. Clin. Cancer Res., 2021, 27(1), 330-341.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-2166] [PMID: 33097495]

Thorsson, V.; Gibbs, D.L.; Brown, S.D.; Wolf, D.; Bortone, D.S.; Ou Yang, T.H.; Porta-Pardo, E.; Gao, G.F.; Plaisier, C.L.; Eddy, J.A.; Ziv, E.; Culhane, A.C.; Paull, E.O.; Sivakumar, I.K.A.; Gentles, A.J.; Malhotra, R.; Farshidfar, F.; Colaprico, A.; Parker, J.S.; Mose, L.E.; Vo, N.S.; Liu, J.; Liu, Y.; Rader, J.; Dhankani, V.; Reynolds, S.M.; Bowlby, R.; Califano, A.; Cherniack, A.D.; Anastassiou, D.; Bedognetti, D.; Mokrab, Y.; Newman, A.M.; Rao, A.; Chen, K.; Krasnitz, A.; Hu, H.; Malta, T.M.; Noushmehr, H.; Pedamallu, C.S.; Bullman, S.; Ojesina, A.I.; Lamb, A.; Zhou, W.; Shen, H.; Choueiri, T.K.; Weinstein, J.N.; Guinney, J.; Saltz, J.; Holt, R.A.; Rabkin, C.S.; Lazar, A.J.; Serody, J.S.; Demicco, E.G.; Disis, M.L.; Vincent, B.G.; Shmulevich, I.; Caesar-Johnson, S.J.; Demchok, J.A.; Felau, I.; Kasapi, M.; Ferguson, M.L.; Hutter, C.M.; Sofia, H.J.; Tarnuzzer, R.; Wang, Z.; Yang, L.; Zenklusen, J.C.; Zhang, J.J.; Chudamani, S.; Liu, J.; Lolla, L.; Naresh, R.; Pihl, T.; Sun, Q.; Wan, Y.; Wu, Y.; Cho, J.; DeFreitas, T.; Frazer, S.; Gehlenborg, N.; Getz, G.; Heiman, D.I.; Kim, J.; Lawrence, M.S.; Lin, P.; Meier, S.; Noble, M.S.; Saksena, G.; Voet, D.; Zhang, H.; Bernard, B.; Chambwe, N.; Dhankani, V.; Knijnenburg, T.; Kramer, R.; Leinonen, K.; Liu, Y.; Miller, M.; Reynolds, S.; Shmulevich, I.; Thorsson, V.; Zhang, W.; Akbani, R.; Broom, B.M.; Hegde, A.M.; Ju, Z.; Kanchi, R.S.; Korkut, A.; Li, J.; Liang, H.; Ling, S.; Liu, W.; Lu, Y.; Mills, G.B.; Ng, K-S.; Rao, A.; Ryan, M.; Wang, J.; Weinstein, J.N.; Zhang, J.; Abeshouse, A.; Armenia, J.; Chakravarty, D.; Chatila, W.K.; de Bruijn, I.; Gao, J.; Gross, B.E.; Heins, Z.J.; Kundra, R.; La, K.; Ladanyi, M.; Luna, A.; Nissan, M.G.; Ochoa, A.; Phillips, S.M.; Reznik, E.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Sheridan, R.; Sumer, S.O.; Sun, Y.; Taylor, B.S.; Wang, J.; Zhang, H.; Anur, P.; Peto, M.; Spellman, P.; Benz, C.; Stuart, J.M.; Wong, C.K.; Yau, C.; Hayes, D.N.; Parker, J.S.; Wilkerson, M.D.; Ally, A.; Balasundaram, M.; Bowlby, R.; Brooks, D.; Carlsen, R.; Chuah, E.; Dhalla, N.; Holt, R.; Jones, S.J.M.; Kasaian, K.; Lee, D.; Ma, Y.; Marra, M.A.; Mayo, M.; Moore, R.A.; Mungall, A.J.; Mungall, K.; Robertson, A.G.; Sadeghi, S.; Schein, J.E.; Sipahimalani, P.; Tam, A.; Thiessen, N.; Tse, K.; Wong, T.; Berger, A.C.; Beroukhim, R.; Cherniack, A.D.; Cibulskis, C.; Gabriel, S.B.; Gao, G.F.; Ha, G.; Meyerson, M.; Schumacher, S.E.; Shih, J.; Kucherlapati, M.H.; Kucherlapati, R.S.; Baylin, S.; Cope, L.; Danilova, L.; Bootwalla, M.S.; Lai, P.H.; Maglinte, D.T.; Van Den Berg, D.J.; Weisenberger, D.J.; Auman, J.T.; Balu, S.; Bodenheimer, T.; Fan, C.; Hoadley, K.A.; Hoyle, A.P.; Jefferys, S.R.; Jones, C.D.; Meng, S.; Mieczkowski, P.A.; Mose, L.E.; Perou, A.H.; Perou, C.M.; Roach, J.; Shi, Y.; Simons, J.V.; Skelly, T.; Soloway, M.G.; Tan, D.; Veluvolu, U.; Fan, H.; Hinoue, T.; Laird, P.W.; Shen, H.; Zhou, W.; Bellair, M.; Chang, K.; Covington, K.; Creighton, C.J.; Dinh, H.; Doddapaneni, H.V.; Donehower, L.A.; Drummond, J.; Gibbs, R.A.; Glenn, R.; Hale, W.; Han, Y.; Hu, J.; Korchina, V.; Lee, S.; Lewis, L.; Li, W.; Liu, X.; Morgan, M.; Morton, D.; Muzny, D.; Santibanez, J.; Sheth, M.; Shinbrot, E.; Wang, L.; Wang, M.; Wheeler, D.A.; Xi, L.; Zhao, F.; Hess, J.; Appelbaum, E.L.; Bailey, M.; Cordes, M.G.; Ding, L.; Fronick, C.C.; Fulton, L.A.; Fulton, R.S.; Kandoth, C.; Mardis, E.R.; McLellan, M.D.; Miller, C.A.; Schmidt, H.K.; Wilson, R.K.; Crain, D.; Curley, E.; Gardner, J.; Lau, K.; Mallery, D.; Morris, S.; Paulauskis, J.; Penny, R.; Shelton, C.; Shelton, T.; Sherman, M.; Thompson, E.; Yena, P.; Bowen, J.; Gastier-Foster, J.M.; Gerken, M.; Leraas, K.M.; Lichtenberg, T.M.; Ramirez, N.C.; Wise, L.; Zmuda, E.; Corcoran, N.; Costello, T.; Hovens, C.; Carvalho, A.L.; de Carvalho, A.C.; Fregnani, J.H.; Longatto-Filho, A.; Reis, R.M.; Scapulatempo-Neto, C.; Silveira, H.C.S.; Vidal, D.O.; Burnette, A.; Eschbacher, J.; Hermes, B.; Noss, A.; Singh, R.; Anderson, M.L.; Castro, P.D.; Ittmann, M.; Huntsman, D.; Kohl, B.; Le, X.; Thorp, R.; Andry, C.; Duffy, E.R.; Lyadov, V.; Paklina, O.; Setdikova, G.; Shabunin, A.; Tavobilov, M.; McPherson, C.; Warnick, R.; Berkowitz, R.; Cramer, D.; Feltmate, C.; Horowitz, N.; Kibel, A.; Muto, M.; Raut, C.P.; Malykh, A.; Barnholtz-Sloan, J.S.; Barrett, W.; Devine, K.; Fulop, J.; Ostrom, Q.T.; Shimmel, K.; Wolinsky, Y.; Sloan, A.E.; De Rose, A.; Giuliante, F.; Goodman, M.; Karlan, B.Y.; Hagedorn, C.H.; Eckman, J.; Harr, J.; Myers, J.; Tucker, K.; Zach, L.A.; Deyarmin, B.; Hu, H.; Kvecher, L.; Larson, C.; Mural, R.J.; Somiari, S.; Vicha, A.; Zelinka, T.; Bennett, J.; Iacocca, M.; Rabeno, B.; Swanson, P.; Latour, M.; Lacombe, L.; Têtu, B.; Bergeron, A.; McGraw, M.; Staugaitis, S.M.; Chabot, J.; Hibshoosh, H.; Sepulveda, A.; Su, T.; Wang, T.; Potapova, O.; Voronina, O.; Desjardins, L.; Mariani, O.; Roman-Roman, S.; Sastre, X.; Stern, M-H.; Cheng, F.; Signoretti, S.; Berchuck, A.; Bigner, D.; Lipp, E.; Marks, J.; McCall, S.; McLendon, R.; Secord, A.; Sharp, A.; Behera, M.; Brat, D.J.; Chen, A.; Delman, K.; Force, S.; Khuri, F.; Magliocca, K.; Maithel, S.; Olson, J.J.; Owonikoko, T.; Pickens, A.; Ramalingam, S.; Shin, D.M.; Sica, G.; Van Meir, E.G.; Zhang, H.; Eijckenboom, W.; Gillis, A.; Korpershoek, E.; Looijenga, L.; Oosterhuis, W.; Stoop, H.; van Kessel, K.E.; Zwarthoff, E.C.; Calatozzolo, C.; Cuppini, L.; Cuzzubbo, S.; DiMeco, F.; Finocchiaro, G.; Mattei, L.; Perin, A.; Pollo, B.; Chen, C.; Houck, J.; Lohavanichbutr, P.; Hartmann, A.; Stoehr, C.; Stoehr, R.; Taubert, H.; Wach, S.; Wullich, B.; Kycler, W.; Murawa, D.; Wiznerowicz, M.; Chung, K.; Edenfield, W.J.; Martin, J.; Baudin, E.; Bubley, G.; Bueno, R.; De Rienzo, A.; Richards, W.G.; Kalkanis, S.; Mikkelsen, T.; Noushmehr, H.; Scarpace, L.; Girard, N.; Aymerich, M.; Campo, E.; Giné, E.; Guillermo, A.L.; Van Bang, N.; Hanh, P.T.; Phu, B.D.; Tang, Y.; Colman, H.; Evason, K.; Dottino, P.R.; Martignetti, J.A.; Gabra, H.; Juhl, H.; Akeredolu, T.; Stepa, S.; Hoon, D.; Ahn, K.; Kang, K.J.; Beuschlein, F.; Breggia, A.; Birrer, M.; Bell, D.; Borad, M.; Bryce, A.H.; Castle, E.; Chandan, V.; Cheville, J.; Copland, J.A.; Farnell, M.; Flotte, T.; Giama, N.; Ho, T.; Kendrick, M.; Kocher, J-P.; Kopp, K.; Moser, C.; Nagorney, D.; O’Brien, D.; O’Neill, B.P.; Patel, T.; Petersen, G.; Que, F.; Rivera, M.; Roberts, L.; Smallridge, R.; Smyrk, T.; Stanton, M.; Thompson, R.H.; Torbenson, M.; Yang, J.D.; Zhang, L.; Brimo, F.; Ajani, J.A.; Gonzalez, A.M.A.; Behrens, C.; Bondaruk, J.; Broaddus, R.; Czerniak, B.; Esmaeli, B.; Fujimoto, J.; Gershenwald, J.; Guo, C.; Lazar, A.J.; Logothetis, C.; Meric-Bernstam, F.; Moran, C.; Ramondetta, L.; Rice, D.; Sood, A.; Tamboli, P.; Thompson, T.; Troncoso, P.; Tsao, A.; Wistuba, I.; Carter, C.; Haydu, L.; Hersey, P.; Jakrot, V.; Kakavand, H.; Kefford, R.; Lee, K.; Long, G.; Mann, G.; Quinn, M.; Saw, R.; Scolyer, R.; Shannon, K.; Spillane, A.; Stretch; Synott, M.; Thompson, J.; Wilmott, J.; Al-Ahmadie, H.; Chan, T.A.; Ghossein, R.; Gopalan, A.; Levine, D.A.; Reuter, V.; Singer, S.; Singh, B.; Tien, N.V.; Broudy, T.; Mirsaidi, C.; Nair, P.; Drwiega, P.; Miller, J.; Smith, J.; Zaren, H.; Park, J-W.; Hung, N.P.; Kebebew, E.; Linehan, W.M.; Metwalli, A.R.; Pacak, K.; Pinto, P.A.; Schiffman, M.; Schmidt, L.S.; Vocke, C.D.; Wentzensen, N.; Worrell, R.; Yang, H.; Moncrieff, M.; Goparaju, C.; Melamed, J.; Pass, H.; Botnariuc, N.; Caraman, I.; Cernat, M.; Chemencedji, I.; Clipca, A.; Doruc, S.; Gorincioi, G.; Mura, S.; Pirtac, M.; Stancul, I.; Tcaciuc, D.; Albert, M.; Alexopoulou, I.; Arnaout, A.; Bartlett, J.; Engel, J.; Gilbert, S.; Parfitt, J.; Sekhon, H.; Thomas, G.; Rassl, D.M.; Rintoul, R.C.; Bifulco, C.; Tamakawa, R.; Urba, W.; Hayward, N.; Timmers, H.; Antenucci, A.; Facciolo, F.; Grazi, G.; Marino, M.; Merola, R.; de Krijger, R.; Gimenez-Roqueplo, A-P.; Piché, A.; Chevalier, S.; McKercher, G.; Birsoy, K.; Barnett, G.; Brewer, C.; Farver, C.; Naska, T.; Pennell, N.A.; Raymond, D.; Schilero, C.; Smolenski, K.; Williams, F.; Morrison, C.; Borgia, J.A.; Liptay, M.J.; Pool, M.; Seder, C.W.; Junker, K.; Omberg, L.; Dinkin, M.; Manikhas, G.; Alvaro, D.; Bragazzi, M.C.; Cardinale, V.; Carpino, G.; Gaudio, E.; Chesla, D.; Cottingham, S.; Dubina, M.; Moiseenko, F.; Dhanasekaran, R.; Becker, K-F.; Janssen, K-P.; Slotta-Huspenina, J.; Abdel-Rahman, M.H.; Aziz, D.; Bell, S.; Cebulla, C.M.; Davis, A.; Duell, R.; Elder, J.B.; Hilty, J.; Kumar, B.; Lang, J.; Lehman, N.L.; Mandt, R.; Nguyen, P.; Pilarski, R.; Rai, K.; Schoenfield, L.; Senecal, K.; Wakely, P.; Hansen, P.; Lechan, R.; Powers, J.; Tischler, A.; Grizzle, W.E.; Sexton, K.C.; Kastl, A.; Henderson, J.; Porten, S.; Waldmann, J.; Fassnacht, M.; Asa, S.L.; Schadendorf, D.; Couce, M.; Graefen, M.; Huland, H.; Sauter, G.; Schlomm, T.; Simon, R.; Tennstedt, P.; Olabode, O.; Nelson, M.; Bathe, O.; Carroll, P.R.; Chan, J.M.; Disaia, P.; Glenn, P.; Kelley, R.K.; Landen, C.N.; Phillips, J.; Prados, M.; Simko, J.; Smith-McCune, K.; VandenBerg, S.; Roggin, K.; Fehrenbach, A.; Kendler, A.; Sifri, S.; Steele, R.; Jimeno, A.; Carey, F.; Forgie, I.; Mannelli, M.; Carney, M.; Hernandez, B.; Campos, B.; Herold-Mende, C.; Jungk, C.; Unterberg, A.; von Deimling, A.; Bossler, A.; Galbraith, J.; Jacobus, L.; Knudson, M.; Knutson, T.; Ma, D.; Milhem, M.; Sigmund, R.; Godwin, A.K.; Madan, R.; Rosenthal, H.G.; Adebamowo, C.; Adebamowo, S.N.; Boussioutas, A.; Beer, D.; Giordano, T.; Mes-Masson, A-M.; Saad, F.; Bocklage, T.; Landrum, L.; Mannel, R.; Moore, K.; Moxley, K.; Postier, R.; Walker, J.; Zuna, R.; Feldman, M.; Valdivieso, F.; Dhir, R.; Luketich, J.; Pinero, E.M.M.; Quintero-Aguilo, M.; Carlotti, C.G., Jr; Dos Santos, J.S.; Kemp, R.; Sankarankuty, A.; Tirapelli, D.; Catto, J.; Agnew, K.; Swisher, E.; Creaney, J.; Robinson, B.; Shelley, C.S.; Godwin, E.M.; Kendall, S.; Shipman, C.; Bradford, C.; Carey, T.; Haddad, A.; Moyer, J.; Peterson, L.; Prince, M.; Rozek, L.; Wolf, G.; Bowman, R.; Fong, K.M.; Yang, I.; Korst, R.; Rathmell, W.K.; Fantacone-Campbell, J.L.; Hooke, J.A.; Kovatich, A.J.; Shriver, C.D.; DiPersio, J.; Drake, B.; Govindan, R.; Heath, S.; Ley, T.; Van Tine, B.; Westervelt, P.; Rubin, M.A.; Lee, J.I.; Aredes, N.D.; Mariamidze, A. The immune landscape of cancer. Immunity, 2018, 48(4), 812-830.e14.
[http://dx.doi.org/10.1016/j.immuni.2018.03.023] [PMID: 29628290]

Wang, Q.; Zhao, Y.; Wang, F.; Tan, G. A novel immune signature predicts immunotherapy responsiveness and reveals the landscape of the tumor immune microenvironment in head and neck squamous cell carcinoma. Front. Genet., 2022, 13, 1051051.
[http://dx.doi.org/10.3389/fgene.2022.1051051] [PMID: 36437964]

Charoentong, P.; Finotello, F.; Angelova, M.; Mayer, C.; Efremova, M.; Rieder, D.; Hackl, H.; Trajanoski, Z. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep., 2017, 18(1), 248-262.
[http://dx.doi.org/10.1016/j.celrep.2016.12.019] [PMID: 28052254]

Angelova, M.; Charoentong, P.; Hackl, H.; Fischer, M.L.; Snajder, R.; Krogsdam, A.M.; Waldner, M.J.; Bindea, G.; Mlecnik, B.; Galon, J.; Trajanoski, Z. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol., 2015, 16(1), 64.
[http://dx.doi.org/10.1186/s13059-015-0620-6] [PMID: 25853550]

Karasaki, T.; Nagayama, K.; Kuwano, H.; Nitadori, J.; Sato, M.; Anraku, M.; Hosoi, A.; Matsushita, H.; Morishita, Y.; Kashiwabara, K.; Takazawa, M.; Ohara, O.; Kakimi, K.; Nakajima, J. An immunogram for the cancer-immunity cycle: Towards personalized immunotherapy of lung cancer. J. Thorac. Oncol., 2017, 12(5), 791-803.
[http://dx.doi.org/10.1016/j.jtho.2017.01.005] [PMID: 28088513]

Sautès-Fridman, C.; Petitprez, F.; Calderaro, J.; Fridman, W.H. Tertiary lymphoid structures in the era of cancer immunotherapy. Nat. Rev. Cancer, 2019, 19(6), 307-325.
[http://dx.doi.org/10.1038/s41568-019-0144-6] [PMID: 31092904]

Teillaud, J.L.; Dieu-Nosjean, M.C. Tertiary lymphoid structures: An anti-tumor school for adaptive immune cells and an antibody factory to fight cancer? Front. Immunol., 2017, 8, 830.
[http://dx.doi.org/10.3389/fimmu.2017.00830] [PMID: 28785261]

Le, X.; Ferrarotto, R.; Wise-Draper, T.; Gillison, M. Evolving role of immunotherapy in recurrent metastatic head and neck cancer. J. Natl. Compr. Canc. Netw., 2020, 18(7), 899-906.
[http://dx.doi.org/10.6004/jnccn.2020.7590] [PMID: 32634775]

Lin, W.; Chen, M.; Hong, L.; Zhao, H.; Chen, Q. Crosstalk between PD-1/PD-L1 blockade and its combinatorial therapies in tumor immune microenvironment: A focus on HNSCC. Front. Oncol., 2018, 8, 532.
[http://dx.doi.org/10.3389/fonc.2018.00532] [PMID: 30519541]

Lechner, A.; Schlößer, H.; Rothschild, S.I.; Thelen, M.; Reuter, S.; Zentis, P.; Shimabukuro-Vornhagen, A.; Theurich, S.; Wennhold, K.; Garcia-Marquez, M.; Tharun, L.; Quaas, A.; Schauss, A.; Isensee, J.; Hucho, T.; Huebbers, C.; von Bergwelt-Baildon, M.; Beutner, D. Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma. Oncotarget, 2017, 8(27), 44418-44433.
[http://dx.doi.org/10.18632/oncotarget.17901] [PMID: 28574843]

Chen, D.S.; Mellman, I. Oncology meets immunology: The cancer-immunity cycle. Immunity, 2013, 39(1), 1-10.
[http://dx.doi.org/10.1016/j.immuni.2013.07.012] [PMID: 23890059]

Pio, R.; Ajona, D.; Ortiz-Espinosa, S.; Mantovani, A.; Lambris, J.D. Complementing the cancer-immunity cycle. Front. Immunol., 2019, 10, 774.
[http://dx.doi.org/10.3389/fimmu.2019.00774] [PMID: 31031765]

Brown, A.L.; Li, M.; Goncearenco, A.; Panchenko, A.R. Finding driver mutations in cancer: Elucidating the role of background mutational processes. PLOS Comput. Biol., 2019, 15(4), e1006981.
[http://dx.doi.org/10.1371/journal.pcbi.1006981] [PMID: 31034466]

Li, J.; Wang, W.; Zhang, Y.; Cieślik, M.; Guo, J.; Tan, M.; Green, M.D.; Wang, W.; Lin, H.; Li, W.; Wei, S.; Zhou, J.; Li, G.; Jing, X.; Vatan, L.; Zhao, L.; Bitler, B.; Zhang, R.; Cho, K.R.; Dou, Y.; Kryczek, I.; Chan, T.A.; Huntsman, D.; Chinnaiyan, A.M.; Zou, W. Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy. J. Clin. Invest., 2020, 130(5), 2712-2726.
[http://dx.doi.org/10.1172/JCI134402] [PMID: 32027624]

Leroy, B.; Anderson, M.; Soussi, T. TP53 mutations in human cancer: Database reassessment and prospects for the next decade. Hum. Mutat., 2014, 35(6), 672-688.
[http://dx.doi.org/10.1002/humu.22552] [PMID: 24665023]

Zhou, G.; Liu, Z.; Myers, J.N. TP53 mutations in head and neck squamous cell carcinoma and their impact on disease progression and treatment response. J. Cell. Biochem., 2016, 117(12), 2682-2692.
[http://dx.doi.org/10.1002/jcb.25592] [PMID: 27166782]

Feng, H.; Yang, F.; Qiao, L.; Zhou, K.; Wang, J.; Zhang, J.; Tian, T.; Du, Y.; Shangguan, H. Prognostic significance of gene signature of tertiary lymphoid structures in patients with lung adenocarcinoma. Front. Oncol., 2021, 11, 693234.
[http://dx.doi.org/10.3389/fonc.2021.693234] [PMID: 34381716]

Outh-Gauer, S.; Morini, A.; Tartour, E.; Lépine, C.; Jung, A.C.; Badoual, C. The microenvironment of head and neck cancers: Papillomavirus involvement and potential impact of immunomodulatory treatments. Head Neck Pathol., 2020, 14(2), 330-340.
[http://dx.doi.org/10.1007/s12105-020-01147-x] [PMID: 32124416]

de Ruiter, E.J.; Mulder, F.J.; Koomen, B.M.; Speel, E.J.; van den Hout, M.F.C.M.; de Roest, R.H.; Bloemena, E.; Devriese, L.A.; Willems, S.M. Comparison of three PD-L1 immunohistochemical assays in head and neck squamous cell carcinoma (HNSCC). Mod. Pathol., 2021, 34(6), 1125-1132.
[http://dx.doi.org/10.1038/s41379-020-0644-7] [PMID: 32759978]

Marletta, S.; Fusco, N.; Munari, E.; Luchini, C.; Cimadamore, A.; Brunelli, M.; Querzoli, G.; Martini, M.; Vigliar, E.; Colombari, R.; Girolami, I.; Pagni, F.; Eccher, A. Atlas of PD-L1 for pathologists: Indications, scores, diagnostic platforms and reporting systems. J. Pers. Med., 2022, 12(7), 1073.
[http://dx.doi.org/10.3390/jpm12071073] [PMID: 35887569]

Anastasiou, M.; Kyriazoglou, A.; Kotsantis, I.; Economopoulou, P.; Kyrkasiadou, M.; Giannopoulou, A.; Kosmidou, A.; Smerdi, D.; Moutafi, M.; Gavrielatou, N.; Psyrri, A. Immune checkpoint inhibitors in sarcomas: A systematic review. Immuno-Oncology and Technology, 2023, 20, 100407.
[http://dx.doi.org/10.1016/j.iotech.2023.100407] [PMID: 38192615]

Lin, Z.; Huang, L.; Li, S.; Gu, J.; Cui, X.; Zhou, Y. Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure. Sci. Rep., 2020, 10(1), 21530.
[http://dx.doi.org/10.1038/s41598-020-78560-3] [PMID: 33299035]