Wang Yaqi, Lu Jiahua, Huang Dandan, Chen Pengju, Shi Jingyi, Cheng Jie, Gan Jingbo, Li Ruifeng, Xu Jingxuan, Gao Zhaoya, Wang Xiaodong, Huang Wensheng, Yin Yanhui, Chen Hebing, Huang Jing, Li Cheng, Gu Jin
Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China.
School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, 100871, China.
BMC Cancer. 2025 Jun 5;25(1):1005. doi: 10.1186/s12885-025-14211-y.
Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth.
A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points.
The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity.
Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes.
肿瘤爆发性生长的特征是在短时间内肿瘤快速生长。目前，对于这种情况尚无精确的科学定义，且其常伴有较差的临床预后。在此，我们报告了一例经历肿瘤爆发性生长的青年结肠癌患者的研究。一个临床多学科团队（MDT）与生物信息学家合作，以提供精准治疗并阐明这种生长背后的生物学机制。
一名28岁被诊断为结肠癌的男性患者经历了肿瘤爆发性生长。在免疫治疗期间采集外周血用于免疫细胞因子分析以及免疫细胞亚群的流式细胞术检测。为进一步探究这种爆发性生长的潜在机制，我们对在不同时间点采集的样本进行了全外显子组测序（WES）和RNA测序（RNA-seq）。
该患者被诊断为林奇综合征。我们实施了免疫治疗，并在治疗前、治疗期间及治疗后进行了外周血免疫细胞因子检测。我们的观察结果表明，免疫治疗可能重塑干扰素-γ（IFN-γ）信号通路并增强T细胞介导的免疫反应。通过探索肿瘤爆发性生长机制，我们观察到肿瘤的插入和缺失（INDEL）突变及INDEL衍生的新抗原显著减少。此外，它们具有抗原呈递功能缺陷，表现为IFN-γ信号活性降低。
新抗原缺失和IFN-γ信号活性降低促成了该患者的肿瘤爆发性生长。恢复的IFN-γ信号通路可能带来有效的免疫治疗效果。
