Heterogeneous tumor-immune microenvironments among differentially growing metastases in an ovarian cancer patient. Homo sapiens

We present an exceptional responder case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesion during a treatment-free period. Using an immunogenomics approach, we found that progressing metastases were infiltrated by CD8+ and CD4+ T cells, exhibited oligoclonal expansion of specific T-cell subsets, and showed indications of neoepitope depletion. These findings imply that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogenous fates of metastatic lesions often observed in the clinic post therapy. The goal of this particular experiment was quantify RNA expression using microarrays, and then evaluate differentially expressed genes and pathways between the different tumor samples. Overall design: Samples analyzed:1) Primary high-grade serous ovarian cancer, 2) Growing spleen metastasis, 3) Shrinking right upper quadrant metastasis, 4) Stable liver metastasis, 5) Growing vaginal cuff metastasis. No control healthy tissues were availabl.e

本研究报道一例高级别浆液性卵巢癌（high-grade serous ovarian cancer）患者的罕见应答病例：该患者接受多线化疗方案治疗后，在无治疗间期内出现部分转移灶消退，同时其余转移灶进展。本研究采用免疫基因组学（immunogenomics）方法开展分析，结果显示进展性转移灶浸润有CD8+和CD4+ T细胞，特定T细胞亚群呈现寡克隆扩增，且存在新表位耗竭迹象。上述结果提示，单一个体内可共存多种截然不同的肿瘤免疫微环境，这在一定程度上可解释临床治疗后转移灶转归常呈现的异质性现象。本实验的核心目标为通过基因芯片（microarrays）定量检测RNA表达水平，进而评估不同肿瘤样本间的差异表达基因及信号通路。实验整体设计：分析样本包括：1）高级别浆液性卵巢癌原发灶；2）进展性脾脏转移灶；3）消退性右上腹转移灶；4）稳定型肝脏转移灶；5）进展性阴道残端转移灶。本研究未获取健康对照组织。