Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2-negative metastatic breast cancer.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-08-06 DOI:10.1007/s00262-024-03782-7
Changhee Park, Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Seock-Ah Im, Min Hwan Kim, Joohyuk Sohn, Jae Ho Jeong, Kyung Hae Jung, Kyoung Eun Lee, Yeon Hee Park, Hee-Jun Kim, Eun Kyung Cho, In Sil Choi, Seung-Jae Noh, Inkyung Shin, Dae-Yeon Cho, Jee Hyun Kim
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Abstract

Background: Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863).

Methods: We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise.

Findings: Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months).

Interpretation: Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.

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与HER-2阴性转移性乳腺癌患者对艾瑞布林和尼夫单抗联合疗法的反应相关的基因组和转录组图谱
背景预测乳腺癌患者对免疫疗法和化疗联合疗法反应的生物标志物尚未确立。在本研究中,我们报告了对参加艾瑞布林和尼夫单抗联合治疗HER-2阴性转移性乳腺癌(MBC)II期临床试验(KORNELIA试验,NCT04061863)的患者的预处理肿瘤组织进行的探索性基因组学和转录组学分析:我们分析了基于基因组(n = 76)和转录组数据(n = 58)的肿瘤分子特征与疗效之间的关联。无进展生存期(PFS)≥6个月的患者定义为PFS6应答者,否则定义为PFS6非应答者:对肿瘤突变负荷(TMB)的分析表明,肿瘤突变负荷对疗效有有利影响,而与同源重组缺陷(HRD)相关的几项分析表明,肿瘤突变负荷对疗效有潜在的负面影响。携带TP53突变的患者的PFS6率和PFS明显较低,这与PFS6无反应者中细胞周期相关特征的富集有关。高抗原呈递基因组富集得分(≥中位数)与较长的PFS显著相关。长期应答者(≥ 18 个月)的新生 B 细胞和浆细胞比例明显更高:解读:包括TMB、HRD和TP53突变在内的基因组特征以及与免疫细胞特征和细胞周期相关的转录组特征可区分应答者。我们的研究结果为进一步探索这些肿瘤的联合治疗方案及其生物标志物提供了启示。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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