Institute of Anatomy, University of Leipzig, Leipzig.
Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany.
Oncoimmunology. 2021 Aug 18;10(1):1960729. doi: 10.1080/2162402X.2021.1960729. eCollection 2021.
Emerging immunotherapies quest for better patient stratification in cancer treatment decisions. Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers urge for meaningful human model systems that allow for investigating immune responses . Here, the standardized patient-derived tissue culture (PDTC) model was applied to investigate tumor response to the PD-1 inhibitor Nivolumab and the CD3/CD28 t-lymphocyte activator ImmunoCult. Resident t-lymphocytes, tumor proliferation and apoptosis, as well as bulk gene expression data were analyzed after 72 h of PD-1 inhibition either as monotherapy or combined with Oxaliplatin or ImmunoCult. Individual responses to PD-1 inhibition were found and combination with chemotherapy or t-lymphocyte activation led to enhanced antitumoral effects in PDTCs. T-lymphocyte activation as well as the addition of pre-cultured peripheral blood mononuclear cells improved PDTC for studying t-lymphocyte and tumor cell communication. These data support the potential of PDTC to investigate immunotherapy in gastric and esophagogastric junction cancer.
新兴的免疫疗法在癌症治疗决策中寻求更好的患者分层。PD-1 抑制在胃癌和胃食管交界处癌症中的中等反应率促使人们需要有意义的人类模型系统来研究免疫反应。在这里，应用标准化的患者衍生组织培养（PDTC）模型来研究 PD-1 抑制剂纳武利尤单抗和 CD3/CD28 T 淋巴细胞激活剂 ImmunoCult 对肿瘤的反应。在 PD-1 抑制作为单药治疗或与奥沙利铂或 ImmunoCult 联合应用 72 小时后，分析了常驻 T 淋巴细胞、肿瘤增殖和凋亡以及批量基因表达数据。发现了对 PD-1 抑制的个体反应，并且联合化疗或 T 淋巴细胞激活导致 PDTC 中抗肿瘤作用增强。T 淋巴细胞激活以及预培养外周血单核细胞的添加改善了 PDTC，以研究 T 淋巴细胞和肿瘤细胞的通信。这些数据支持 PDTC 用于研究胃癌和胃食管交界处癌症的免疫疗法的潜力。
