CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
HER2 阳性乳腺癌的免疫组库及对新辅助 TCHP 治疗的应答
英文原题：Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer.
查看英文原题
Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer.
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研究概要
尚未明确 TCR 和 BCR 库的多样性、丰富度和密度作为 TCHP 疗效预测标志物的作用。
中文摘要
尽管已引入 trastuzumab，约 30%–40% 的人表皮生长因子受体 2 阳性乳腺癌患者仍未达到病理完全缓解（pCR）。TIL（肿瘤浸润淋巴细胞）被认为是治疗反应的预测标志物，但预测效果并非总是理想。我们研究 trastuzumab、docetaxel、carboplatin 和 pertuzumab（TCHP）治疗与免疫组库之间的关系，评估其预测治疗反应的作用。 设计：共纳入 35 例病例，分为两个实验组：预备实验 10 例，主要实验 25 例。预备实验比较 TCHP 治疗前活检组织和治疗后手术组织；主要实验根据 TCHP 治疗反应比较治疗前活检组织。
评估 T 细胞受体组库 TRA、TRB、TRG 和 TRD，以及 B 细胞受体组库免疫球蛋白重链、κ 链和 λ 链，并进行全转录组测序。
预备实验中，无论 TCHP 治疗反应如何，治疗后 T 细胞受体（TCR）和 B 细胞受体（BCR）组库的密度和丰富度均下降。主要实验中，达到和未达到 pCR 患者的 TCR 和 BCR 组库 Shannon 熵指数、密度及 CDR3 长度均无显著差异。按 TIL 水平分层后比较 pCR 和非 pCR 亚组，非 pCR/低 TIL 组中低频克隆比例高于 pCR/低 TIL 组：TRA 克隆频率 0.01%–0.1% 分别为 63% 和 45.3%，<0.01% 分别为 32.9% 和 51.8%（P<0.001）；TRB 克隆频率 0.01%–0.1% 分别为 26.5% 和 14.7%，<0.01% 分别为 72.0% 和 84.1%（P<0.001）。
尚未发现 TCR 和 BCR 组库多样性、丰富度及密度可作为 TCHP 治疗反应预测标志物。低频克隆组成可能是 TCHP 反应的候选预测因素，但仍需验证研究和进一步调查。
展开英文摘要原文
Despite the introduction of trastuzumab, pathologic complete response (pCR) is not attained in approximately 30-40% of Human epithelial growth factor receptor-2-positive breast cancer. Tumor-infiltrating lymphocytes (TIL) have been suggested as a predictive marker of treatment response, albeit not always effective. We investigated the relationship between trastuzumab, docetaxel, carboplatin, and pertuzumab (TCHP) treatment and immune repertoire as a treatment response predictor. DESIGN: In all, 35 cases were divided into two experimental groups: 10 and 25 cases in the preliminary and main experiments, respectively. In the preliminary experiment, the biopsy tissues before TCHP treatment and the surgical tissues after TCHP treatment were compared. In the main experiment, the biopsy tissues before TCHP treatment were compared according to the TCHP treatment response.
The T-cell repertoire for TRA, TRB, TRG, and TRD, and B-cell repertoire for immunoglobulin heavy, immunoglobulin kappa, and immunoglobulin lambda were evaluated. Whole transcriptome sequencing was also performed.
In the preliminary experiment, the density and richness of the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires decreased after treatment, regardless of TCHP response. In the main experiment, the Shannon's entropy index, density, and length of CDR3 of the TCR and BCR repertoires did not differ significantly in patients who did and did not achieve pCR. The pCR and non-pCR subgroups according to the level of TILs revealed that the non-pCR/lowTIL group had a higher proportion of low-frequency clones than the pCR/lowTIL group in TRA (non-pCR/lowTIL versus pCR/lowTIL, 0.01-0.1%, 63% versus 45.3%; <0.01%, 32.9% versus 51.8%, p < 0.001) and TRB (non-pCR/lowTIL versus pCR/lowTIL, 0.01-0.1%, 26.5% versus 14.7%; <0.01%, 72.0% versus 84.1%, p < 0.001).
The role of the diversity, richness, and density of the TCR and BCR repertoires as predictive markers for TCHP response was not identified. Compositions of low-frequency clones could be candidates for predictive factors of TCHP response; however, validation studies and further research are necessary.
论文信息
- 作者
- Shin J、Ham B、Seo JH、Lee SB、Park IA、Gong G、Kim SB、Lee HJ
- 第一作者单位
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.South Korea
- 通讯作者单位
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.South Korea
- 期刊
- Therapeutic advances in medical oncology2023
- 原文标识
- PubMed 36865681 · DOI 10.1177/17588359231157654
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