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However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers\u2019 attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side effects of CAR-T cell therapy against HNSCC are barriers to clinical translation. The limited choices of targeting proteins, the barriers of CAR-T cell infiltration into targeted tumors and short survival time in vivo should be solved. In this review, we introduce barriers of CAR-T cell therapy in HNSCC. The limitations and current promising strategies to overcome barriers in solid tumors, as well as the applications for HNSCC treatment, are covered. The perspectives of CAR-T cell therapy in future HNSCC treatment are also discussed.<\/jats:p>","DOI":"10.3390\/jcm12062173","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T03:03:57Z","timestamp":1678676637000},"page":"2173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Han-Qi","family":"Wang","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"},{"name":"Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxing","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, University of California, Los Angeles, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8478-2086","authenticated-orcid":false,"given":"Qi-Wen","family":"Man","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"},{"name":"Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"},{"name":"Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4324-1640","authenticated-orcid":false,"given":"Lin-Lin","family":"Bu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"},{"name":"Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. 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