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:Phenotypic Analysis of 26 Cultured TILs Derived From Japanese Melanoma Tissues.
Phenotypic Analysis of 26 Cultured TILs Derived From Japanese Melanoma Tissues.
本研究首次对从一系列日本黑色素瘤患者中建立培养的TIL进行了特征描述。这些发现表明,从日本黑色素瘤组织中扩增肿瘤反应性TIL是可行的,并可能为日本TIL疗法的发展提供基础。
TIL(肿瘤浸润淋巴细胞)疗法作为一种有前景的下一代癌症免疫疗法,日益受到关注,可能克服当前免疫检查点抑制剂的一些局限性。然而,源自日本黑色素瘤组织的TIL的表型特征和肿瘤反应性仍研究不足。本研究旨在评估从日本黑色素瘤标本中扩增TIL的可行性,并表征其表型及自体肿瘤反应性。
TIL从26例日本黑色素瘤标本中扩增,包括来源于原发性和黏膜病变的肿瘤。评估了培养TIL的表型,并在9份可获得的TIL样本中评估了针对自体肿瘤细胞的反应性。
TIL成功从日本黑色素瘤组织中扩增,这与美国此前的报道一致。培养的TIL表型在各病例间差异显著。在9份检测抗自体肿瘤细胞反应性的TIL样本中,7份检测到MHC I类限制性特异性反应性,包括1份来源于黏膜黑色素瘤的样本。未观察到抗自体肿瘤反应性与CD3+CD8+T细胞比例或CD3+CD8+T细胞上特定标志物表达之间存在明确关联。
PURPOSE: Tumor-infiltrating lymphocyte (TIL) therapy has attracted increasing attention as a promising next-generation cancer immunotherapy that may overcome some limitations of current immune checkpoint inhibitors. However, the phenotypic characteristics and tumor reactivity of TILs derived from Japanese melanoma tissues remain insufficiently investigated. This study aimed to evaluate the feasibility of expanding TILs from Japanese melanoma specimens and to characterize their phenotype and autologous tumor reactivity. METHODS: TILs were expanded from 26 Japanese melanoma specimens, including tumors derived from primary and mucosal lesions. The phenotypes of cultured TILs were assessed, and reactivity against autologous tumor cells was evaluated in 9 available TIL samples. RESULTS: TILs were successfully expanded from Japanese melanoma tissues, consistent with previous reports from the United States. The phenotypes of cultured TILs varied substantially among cases. Among the 9 TIL samples tested for reactivity against autologous tumor cells, MHC class I-restricted specific reactivity was detected in 7 samples, including 1 sample derived from mucosal melanoma. No clear association was observed between autologous tumor reactivity and the proportion of CD3 + CD8 + T cells or the expression of specific markers on CD3 + CD8 + T cells. CONCLUSION: This study is the first to characterize cultured TILs established from a series of Japanese melanoma patients. These findings suggest that the expansion of tumor-reactive TILs from Japanese melanoma tissues is feasible and may provide a basis for the development of TIL therapy in Japan.
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