Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Prim. 2020;6:92.
Google ScholarÂ
Cramer JD, Burtness B, Le QT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16:669–83.
Google ScholarÂ
Li B, Xie S, Han J, Cao H, Lin Z, Hu H, et al. Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study. Int J Surg. 2025;111:781–90.
Sabando-Criollo K, Fernández-Cuya MS, Lozano-Burgos C, MartÃnez-Flores R, González-Arriagada WA. Nonmetastatic lymph node histological architecture is associated with metastasis, recurrence, and survival in oral squamous cell carcinoma. J Oral Pathol Med. 2025;54:371–9.
Google ScholarÂ
Van den Bossche V, Zaryouh H, Vara-Messler M, Vignau J, Machiels J-P, Wouters A, et al. Microenvironment-driven intratumoral heterogeneity in head and neck cancers: clinical challenges and opportunities for precision medicine. Drug Resist Updat. 2022;60:100806.
Google ScholarÂ
Chinn SB, Myers JN. Oral cavity carcinoma: current management, controversies, and future directions. J Clin Oncol. 2015;33:3269–76.
Google ScholarÂ
Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, et al. NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022. J Natl Compr Canc Netw. 2022;20:224–34.
Google ScholarÂ
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. 2019;394:1915–28.
Google ScholarÂ
Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, et al. Neoadjuvant and adjuvant pembrolizumab in locally advanced head and neck cancer. N Engl J Med. 2025;393:37–50.
Google ScholarÂ
Huang Y, Sun J, Li J, Zhu D, Dong M, Dou S, et al. Neoadjuvant immunochemotherapy for locally advanced resectable oral squamous cell carcinoma: a prospective single-arm trial (Illuminate Trial). Int J Surg. 2023;109:2220–7.
Google ScholarÂ
Liu H-M, Xiong X-P, Yu Z-L, Shao Z, Chen G-L, Liu Y-T, et al. Neoadjuvant immunotherapy with or without chemotherapy in locally advanced oral squamous cell carcinoma: randomized, two-arm, phase 2 trial. Cell Rep Med. 2025;6:101930.
Google ScholarÂ
Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586–97.
Google ScholarÂ
Millen R, De Kort WWB, Koomen M, van Son GJF, Gobits R, Penning de Vries B, et al. Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification. Med. 2023;4:290–310.e212.
Driehuis E, Kolders S, Spelier S, Lõhmussaar K, Willems SM, Devriese LA, et al. Oral mucosal organoids as a potential platform for personalized cancer therapy. Cancer Discov. 2019;9:852–71.
Google ScholarÂ
Fisch A-S, Pestana A, Sachse V, Doll C, Hofmann E, Heiland M, et al. Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma. Eur J Cancer. 2024;213:115100.
Google ScholarÂ
Polak R, Zhang ET, Kuo CJ. Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment. Nat Rev Cancer. 2024;24:523–39.
Google ScholarÂ
Xu H, Jiao D, Liu A, Wu K. Tumor organoids: applications in cancer modeling and potentials in precision medicine. J Hematol Oncol. 2022;15:58.
Google ScholarÂ
Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL, Ju J, et al. Organoid modeling of the tumor immune microenvironment. Cell. 2018;175:1972-88.e1916.
Zhang J, Tavakoli H, Ma L, Li X, Han L, Li X. Immunotherapy discovery on tumor organoid-on-a-chip platforms that recapitulate the tumor microenvironment. Adv Drug Deliv Rev. 2022;187:114365.
Google ScholarÂ
Zhao H, Jiang E, Shang Z. 3D Co-culture of cancer-associated fibroblast with oral cancer organoids. J Dent Res. 2021;100:201–8.
Google ScholarÂ
Dijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell. 2018;174:1586–98.e1512.
Tsai S, McOlash L, Palen K, Johnson B, Duris C, Yang Q, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer. 2018;18:335.
Google ScholarÂ
Zhou G, Lieshout R, van Tienderen GS, de Ruiter V, van Royen ME, Boor PPC, et al. Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells. Br J Cancer. 2022;127:649–60.
Google ScholarÂ
Liu J, Li P, Wang L, Li M, Ge Z, Noordam L, et al. Cancer-associated fibroblasts provide a stromal niche for liver cancer organoids that confers trophic effects and therapy resistance. Cell Mol Gastroenterol Hepatol. 2021;11:407–31.
Google ScholarÂ
Schuth S, Le Blanc S, Krieger TG, Jabs J, Schenk M, Giese NA, et al. Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system. J Exp Clin Cancer Res. 2022;41:312.
Google ScholarÂ
Sase M, Sato T, Sato H, Miya F, Zhang S, Haeno H, et al. Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease. Dev Cell. 2025;60:396-413.e396.
Gan J, Meng W, Yang D, Feng X, Zhu G. Comparative analysis of patient-derived organoids among oral squamous cell carcinoma and mucosa identifies the distinct features. Arch Oral Biol. 2026;184:106520.
Google ScholarÂ
Lee MR, Kang S, Lee J, Kong S-Y, Kim Y, Lee Y-S, et al. Organoid morphology-guided classification for oral cancer reveals prognosis. Cell Rep Med. 2025;6:102129.
Google ScholarÂ
Choi SY, Shim J, Gu D-e, Kim SY, Kim HJ, Shin D-Y, et al. Clonal evolution of long-term expanding head and neck cancer organoid: impact on treatment response for personalized therapeutic screening. Oral Oncol. 2023;146:106571.
Google ScholarÂ
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol. 2016;2:46–54.
Google ScholarÂ
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3:1051–8.
Google ScholarÂ
Sha D, Jin Z, Budczies J, Kluck K, Stenzinger A, Sinicrope FA. Tumor mutational burden as a predictive biomarker in solid tumors. Cancer Discov. 2020;10:1808–25.
Google ScholarÂ
Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.
Google ScholarÂ
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.
Google ScholarÂ
Zhang H, Yue X, Chen Z, Liu C, Wu W, Zhang N, et al. Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials. Mol Cancer. 2023;22:159.
Google ScholarÂ
Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 2021;18:792–804.
Google ScholarÂ
Farin HF, Mosa MH, Ndreshkjana B, Grebbin BM, Ritter B, Menche C, et al. Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses. Cancer Discov. 2023;13:2192–211.
Google ScholarÂ
Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171:1611–24.e1624.
Ma Z, Li X, Mao Y, Wei C, Huang Z, Li G, et al. Interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via WNT5A in bladder cancer. Cancer Cell. 2022;40:1550–65.e1557.

