单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma.
过去三十年间,人乳头状瘤病毒(HPV)相关口咽鳞状细胞癌(OPSCC)的发病率大幅上升,自2017年起,AJCC分期系统已将其确认为与HPV阴性对应类型不同的独立病种。
过去三十年间,人乳头瘤病毒(HPV)相关口咽鳞状细胞癌(OPSCC)发病率显著上升;自2017年以来,AJCC分期系统已将其认定为有别于HPV阴性肿瘤的独立类型。HPV相关癌变机制、肿瘤微环境及宿主免疫应答,为治疗开发提供了机会。虽然抗PD-1免疫疗法已成为复发或转移性头颈部鳞状细胞癌(HNSCC)总体治疗标准的一部分,但针对HPV相关HNSCC尚无确立的免疫治疗策略。目前正在积极研究多种新兴方法,包括单用或联合抗PD-(L)1佐剂的治疗性疫苗、基于肽–HLA的免疫疗法平台,以及TIL(肿瘤浸润淋巴细胞)疗法、T细胞受体(TCR)疗法和嵌合抗原受体(CAR)T细胞疗法等过继细胞疗法。除了进一步完善这些新型免疫治疗策略外,还需开展更多工作,以明确其最佳应用疾病阶段(局限性或复发/转移性),并开发靶向HPV特异性病毒致癌机制的小分子抑制剂。
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied-among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide-HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis.
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