免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Salvage Metastasectomy After Adoptive Cell Transfer for Melanoma: Long-Term Updates.
Salvage Metastasectomy After Adoptive Cell Transfer for Melanoma: Long-Term Updates.
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过继性细胞转移(ACT)可在转移性黑色素瘤患者中诱导持久缓解,部分初始缓解的患者可能出现疾病进展,需要挽救治疗。
我们报告了对2000年至2022年在单一机构接受ACT的转移性黑色素瘤患者进行回顾性审查的最新随访结果。我们确定了在出现颅外最多三个部位的寡进展并接受手术治疗之前,具有客观缓解(RECIST 1.0)或疾病稳定至少6个月(SD6)的患者。主要结局是手术后的无进展生存期(PFS)和总生存期(OS)。我们还对肿瘤逃逸的基因组机制进行了探索性分析。
共有138例接受ACT治疗的转移性黑色素瘤患者在疾病进展前出现客观缓解或SD6。其中,30例(21%)出现颅外寡进展并接受了转移灶切除术治疗。中位随访时间为132个月(范围5-248),中位OS未达到,中位PFS为10.5个月。10年OS为54.7%,并在6年后进入平台期。4例具有ACT治疗前后肿瘤测序数据的患者显示出显著的突变演化,其中1例患者丢失了两个主要组织相容性复合体I类限制性新抗原,这两个新抗原可被原始输注产物中的T细胞识别。
在初始对ACT(完全缓解、部分缓解或SD6)有反应后出现寡进展的患者中,27%通过手术治疗获得了持久疾病控制,证实了对于ACT后可能并不预示全身性失败的“局部”失败,手术是一种潜在可行的挽救选择。与ACT反应和寡进展相关的、可能指导挽救性转移灶切除术患者选择的额外因素仍未明确。
Adoptive cell transfer (ACT) can mediate durable regression in patients with metastatic melanoma, and some patients with initial response may progress, requiring salvage therapy.
We report updated follow-up on a retrospective review of patients with metastatic melanoma receiving ACT at a single institution from 2000 to 2022. We identified patients with objective response (RECIST 1.0) or stable disease for at least 6 months (SD6) before experiencing oligoprogression in up to three extracranial sites managed with surgery. The primary outcomes were progression-free survival (PFS) and overall survival (OS) after surgery. We also performed an exploratory analysis for genomic mechanisms of tumor escape.
In total, 138 patients with metastatic melanoma treated with ACT had an objective response or SD6 before experiencing disease progression. Of these, 30 (21%) had extracranial oligoprogression managed with metastasectomy. With a median follow-up of 132 months (range 5-248), median OS was not reached and median PFS was 10.5 months. Ten-year OS was 54.7% and plateaued after 6 years. Four patients with pre- and post-ACT tumor sequencing demonstrated significant mutational evolution, with one patient experiencing loss of two major histocompatibility complex class I-restricted neoantigens recognized by T cells in the original infusion product.
Of patients experiencing oligoprogression after initial response to ACT (complete response, partial response, or SD6), 27% derived durable disease control after surgical management, confirming a potentially viable salvage option for "local" failures following ACT that may not portend systemic failure. Additional factors related to ACT response and oligoprogression that may guide patient selection for salvage metastasectomy remain undefined.
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