Burtness, Harrington B, Greil KJ, Soulières R, Tahara D, de Castro M, 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. https://doi.org/10.1016/s0140-6736(19)32591-7.
Google Scholar
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. https://doi.org/10.1056/NEJMoa2415434.
Google Scholar
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. https://doi.org/10.1097/js9.0000000000000489.
Google Scholar
Zhang Z, Wu B, Peng G, Xiao G, Huang J, Ding Q, et al. Neoadjuvant chemoimmunotherapy for the treatment of locally advanced head and neck squamous cell carcinoma: a single-arm phase 2 clinical trial. Clin Cancer Res. 2022;28:3268–76. https://doi.org/10.1158/1078-0432.Ccr-22-0666.
Google Scholar
Fang Q, Xu P, Cao F, Wu D, Liu X. PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study. Cancer Immunol Immunother. 2023;72:4161–8. https://doi.org/10.1007/s00262-023-03550-z.
Google Scholar
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. https://doi.org/10.1097/js9.0000000000001891.
Google Scholar
Ren S, Lan T, Wu F, Chen S, Jiang X, Huo C, et al. Intratumoral CD103(+) CD8(+) T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma. Cancer Commun. 2023;43:1143–63. https://doi.org/10.1002/cac2.12480.
Google Scholar
Yang R, Cheng S, Luo N, Gao R, Yu K, Kang B, et al. Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis. Genome Biol. 2019;21:2. https://doi.org/10.1186/s13059-019-1921-y.
Google Scholar
Eiva MA, Omran DK, Chacon JA, Powell DJ Jr. Systematic analysis of CD39, CD103, CD137, and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs. Eur J Immunol. 2022;52:96–108. https://doi.org/10.1002/eji.202149329.
Google Scholar
Laumont CM, Wouters MCA, Smazynski J, Gierc NS, Chavez EA, Chong LC, et al. Single-cell profiles and prognostic impact of tumor-infiltrating lymphocytes coexpressing CD39, CD103, and PD-1 in ovarian cancer. Clin Cancer Res. 2021;27:4089–4100. https://doi.org/10.1158/1078-0432.Ccr-20-4394.
Google Scholar
van den Bulk, J, van der Ploeg, M, Ijsselsteijn, ME, Ruano, D, van der Breggen, R, Duhen, R et al. CD103 and CD39 coexpression identifies neoantigen-specific cytotoxic T cells in colorectal cancers with low mutation burden. J Immunother Cancer 11, https://doi.org/10.1136/jitc-2022-005887 (2023).
Duhen T, Duhen R, Montler R, Moses J, Moudgil T, de Miranda NF, et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun. 2018;9:2724. https://doi.org/10.1038/s41467-018-05072-0.
Google Scholar
Ju WT, Liu Y, Wang LZ, Li J, Ren GX, Sun J, et al. Phase III trial of docetaxel cisplatin 5-fluorouracil induction chemotherapy for resectable oral cancer suggests favorable pathological response as a surrogate endpoint for good therapeutic outcome. Cancer Commun (Lond). 2021;41:279–83. https://doi.org/10.1002/cac2.12136.
Google Scholar
Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol. 2018;29:1853–60. https://doi.org/10.1093/annonc/mdy218.
Google Scholar
Hellmann MD, Chaft JE, William WN, Rusch V, Pisters KM, Kalhor N, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 2014;15:e42–50. https://doi.org/10.1016/s1470-2045(13)70334-6.
Google Scholar
Ye Y, Wu F, Li B, Ma H, Mai L, Peng Y, et al. Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway. BMC Oral Health. 2025;25:840. https://doi.org/10.1186/s12903-025-06082-3.
Google Scholar
Wang Y, Wang R, Li B, Huang Z, Zhao S, Chen S, et al. Cancer-associated fibroblasts in the invasive tumour front promote the metastasis of oral squamous cell carcinoma through MFAP5 upregulation. Gene. 2023;876:147504. https://doi.org/10.1016/j.gene.2023.147504.
Google Scholar
Cha JH, Yang WH, Xia W, Wei Y, Chan LC, Lim SO, et al. Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1. Mol Cell. 2018;71:606–e607. https://doi.org/10.1016/j.molcel.2018.07.030.
Google Scholar
Li B, Ding Y, Huo C, Ren S, Chen S, He H, et al. Targeting Circ-OCAC suppress oral squamous cell carcinoma progression. Oral Dis. 2024;30:2202–18. https://doi.org/10.1111/odi.14687.
Google Scholar
Galbo PM Jr, Zang X, Zheng D. Molecular features of cancer-associated fibroblast subtypes and their implication on cancer pathogenesis, prognosis, and immunotherapy resistance. Clin Cancer Res. 2021;27:2636–47. https://doi.org/10.1158/1078-0432.Ccr-20-4226.
Google Scholar
Xiao Z, Todd L, Huang L, Noguera-Ortega E, Lu Z, Huang L, et al. Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors. Nat Commun. 2023;14:5110. https://doi.org/10.1038/s41467-023-40850-5.
Google Scholar
Zheng B, Qu J, Ohuchida K, Feng H, Chong SJF, Yan Z, et al. LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of pancreatic cancer. Theranostics. 2020;10:10274–89. https://doi.org/10.7150/thno.47001.
Google Scholar
El-Asady R, Yuan R, Liu K, Wang D, Gress RE, Lucas PJ, et al. TGF-{beta}-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease. J Exp Med. 2005;201:1647–57. https://doi.org/10.1084/jem.20041044.
Google Scholar
Canale FP, Ramello MC, Núñez N, Araujo Furlan CL, Bossio SN, Gorosito Serrán M, et al. CD39 expression defines cell exhaustion in tumor-infiltrating CD8(+) T cells. Cancer Res. 2018;78:115–28. https://doi.org/10.1158/0008-5472.Can-16-2684.
Google Scholar
Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–29. https://doi.org/10.1016/j.devcel.2008.05.009.
Google Scholar
O’Connell JT, Sugimoto H, Cooke VG, MacDonald BA, Mehta AI, LeBleu VS, et al. VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc Natl Acad Sci USA. 2011;108:16002–7. https://doi.org/10.1073/pnas.1109493108.
Google Scholar
Zeng F, Gao M, Liao S, Zhou Z, Luo G, Zhou Y. Role and mechanism of CD90(+) fibroblasts in inflammatory diseases and malignant tumors. Mol Med. 2023;29:20. https://doi.org/10.1186/s10020-023-00616-7.
Google Scholar
Valdivia A, Avalos AM, Leyton L. Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways. Front Cell Dev Biol. 2023;11:1221306. https://doi.org/10.3389/fcell.2023.1221306.
Google Scholar
Couchman, JR Syndecan-1 (CD138), Carcinomas and EMT. Int J Mol Sci 22, https://doi.org/10.3390/ijms22084227 (2021).
Wragg JW, Finnity JP, Anderson JA, Ferguson HJ, Porfiri E, Bhatt RI, et al. MCAM and LAMA4 are highly enriched in tumor blood vessels of renal cell carcinoma and predict patient outcome. Cancer Res. 2016;76:2314–26. https://doi.org/10.1158/0008-5472.Can-15-1364.
Google Scholar
Liu Y, Xu Y, Ding L, Yu L, Zhang B, Wei D. LncRNA MEG3 suppressed the progression of ovarian cancer via sponging miR-30e-3p and regulating LAMA4 expression. Cancer Cell Int. 2020;20:181. https://doi.org/10.1186/s12935-020-01259-y.
Google Scholar
Peng L, Li Y, Wei S, Li X, Dang Y, Zhang W, et al. LAMA4 activated by Androgen receptor induces the cisplatin resistance in gastric cancer. Biomed Pharmacother Biomed Pharmacotherapie. 2020;124:109667. https://doi.org/10.1016/j.biopha.2019.109667.
Google Scholar
Li, L, Shirkey, MW, Zhang, T, Piao, W, Li, X, Zhao, J et al. Lymph node fibroblastic reticular cells preserve a tolerogenic niche in allograft transplantation through laminin α4. J Clin Investig 132, https://doi.org/10.1172/jci156994 (2022).
Zhang J, Li Z, Zhang Q, Ma W, Fan W, Dong J, et al. LAMA4(+) CD90(+) eCAFs provide immunosuppressive microenvironment for liver cancer through induction of CD8(+) T cell senescence. Cell Commun Signal : CCS. 2025;23:203. https://doi.org/10.1186/s12964-025-02162-7.
Google Scholar

