研究概要
这些数据表明TMB与CD8+ TIL密度的独立性,以及ARID1A改变参与接受放疗的宫颈癌患者的抗肿瘤免疫反应,值得进一步的机制研究和前瞻性验证。
中文摘要
背景:肿瘤突变负荷(TMB)和基质中的CD8阳性TIL(肿瘤浸润淋巴细胞)(CD8⁺ TIL)在放疗抗肿瘤免疫应答中发挥重要作用。本研究旨在阐明接受放疗的宫颈癌患者中,TMB、CD8⁺ TIL与临床因素之间的关联。方法:回顾性纳入接受根治性放疗的宫颈鳞状细胞癌患者;患者须有相同肿瘤组织的体细胞突变数据和免疫组织化学染色数据。分析TMB和/或CD8⁺ TIL密度与患者特征、突变谱及治疗结局之间的关联。结果:研究分析44例患者,中位随访61个月。TMB与CD8⁺ TIL密度之间,以及TMB或CD8⁺ TIL密度与患者特征之间均无显著相关性。TMB高或CD8⁺ TIL密度低与总生存期和无远处转移生存期较差相关;联合使用这两项指标时,预测价值更高。TMB高或CD8⁺ TIL密度高与ARID1A突变相关。结论:这些数据表明,在接受放疗的宫颈癌患者中,TMB与CD8⁺ TIL密度相互独立,且ARID1A改变参与抗肿瘤免疫应答;这值得进一步开展机制研究和前瞻性验证。
展开英文摘要原文
BACKGROUND: Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8 + TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8 + TILs, and clinical factors in patients with cervical cancer treated with radiotherapy.
METHODS: Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mutation data and immunohistochemical staining data from identical tumor tissues, were enrolled retrospectively. The association between TMB and/or CD8 + TIL density and patient characteristics, mutation profiles, and treatment outcome was analyzed.
RESULTS: The study analyzed 44 patients (median follow-up period, 61 months). There was no significant correlation between TMB and CD8 + TIL density, or between TMB or CD8 + TIL density and patient characteristics. TMB-high or CD8 + TIL density-low status was associated with worse overall survival and distant metastasis-free survival; the predictive value of these factors became greater when used in combination. TMB-high or CD8 + TIL density-high status was associated with ARID1A mutations.
CONCLUSIONS: These data indicate independence of TMB and CD8 + TIL density and the involvement of ARID1A alterations in antitumor immune responses in patients with cervical cancers treated with radiotherapy, warranting further mechanistic research and prospective validation.
论文信息
- 作者
- Ruan H、Oike T、Sato H、Ando K、Ohno T
- 单位
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi 371-8511, Gunma, Japan.Japan
- 期刊
- Cancers2023 Feb 14