Evaluation of cancer immunotherapy using mini-tumor chips.
Evaluation of cancer immunotherapy using mini-tumor chips.
复制标题
作者：
Ao Z;Cai H;Wu Z;Hu L;Li X;Kaurich C;Gu M;Cheng L;Lu X;Guo F
基本原理：预测肿瘤对辅助治疗的反应可能有助于指导治疗决策并提高患者生存率。目前，肿瘤病理学、组织学和分子谱正被整合到个性化谱中，以指导治疗决策。然而，评估肿瘤对免疫治疗的反应以用于个性化医学仍然是一个巨大的挑战。方法：我们提出了一种基于微流体的微型肿瘤芯片方法，用于在临床前模型中预测肿瘤对癌症免疫治疗的反应。通过将解离的肿瘤细胞均匀地输注到分离的微流体孔阵列中，可以在芯片上均匀地产生960个微型肿瘤，每个孔代表保留原始肿瘤细胞组成和动态细胞-细胞相互作用以及自分泌/旁分泌细胞因子的离体肿瘤小生境。结果如下：通过结合延时活细胞成像，我们的微型肿瘤芯片允许研究动态免疫-肿瘤相互作用以及它们对癌症免疫治疗的反应（例如，抗PD 1治疗）。此外，通过建立具有组成性差异PD-L1表达水平的原位乳腺肿瘤模型，我们表明，早在肿瘤接种后10天就对原发性肿瘤对抗PD 1的反应进行芯片上询问可以预测在第24天终点时体内肿瘤对抗PD 1的反应。我们还展示了这种微型肿瘤芯片的应用，以询问从原发性人乳腺癌和肾肿瘤组织中分离的原发性肿瘤细胞的芯片上反应。结论：我们的方法提供了一种简单，快速的解决方案来测量肿瘤对癌症免疫治疗的反应。
Rationale: Predicting tumor responses to adjuvant therapies can potentially help guide treatment decisions and improve patient survival. Currently, tumor pathology, histology, and molecular profiles are being integrated into personalized profiles to guide therapeutic decisions. However, it remains a grand challenge to evaluate tumor responses to immunotherapy for personalized medicine. Methods: We present a microfluidics-based mini-tumor chip approach to predict tumor responses to cancer immunotherapy in a preclinical model. By uniformly infusing dissociated tumor cells into isolated microfluidic well-arrays, 960 mini-tumors could be uniformly generated on-chip, with each well representing the ex vivo tumor niche that preserves the original tumor cell composition and dynamic cell-cell interactions and autocrine/paracrine cytokines. Results: By incorporating time-lapse live-cell imaging, our mini-tumor chip allows the investigation of dynamic immune-tumor interactions as well as their responses to cancer immunotherapy (e.g., anti-PD1 treatment) in parallel within 36 hours. Additionally, by establishing orthotopic breast tumor models with constitutive differential PD-L1 expression levels, we showed that the on-chip interrogation of the primary tumor's responses to anti-PD1 as early as 10 days post tumor inoculation could predict the in vivo tumors' responses to anti-PD1 at the endpoint of day 24. We also demonstrated the application of this mini-tumor chip to interrogate on-chip responses of primary tumor cells isolated from primary human breast and renal tumor tissues. Conclusions: Our approach provides a simple, quick-turnaround solution to measure tumor responses to cancer immunotherapy.
登录
查看更多内容
影响因子：
8.8
作者：
Guo F;Li S;Caglar MU;Mao Z;Liu W;Woodman A;Arnold JJ;Wilke CO;Huang TJ;Cameron CE
通讯作者：
Cameron CE
DOI：
10.1056/nejmoa2108873
发表时间：
2021-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.6
作者：
Ayuso JM;Rehman S;Virumbrales-Munoz M;McMinn PH;Geiger P;Fitzgerald C;Heaster T;Skala MC;Beebe DJ
通讯作者：
Beebe DJ
影响因子：
10.1
作者：
Schrand B;Berezhnoy A;Brenneman R;Williams A;Levay A;Kong LY;Rao G;Zhou S;Heimberger AB;Gilboa E
通讯作者：
Gilboa E
影响因子：
64.5
作者：
Neal, James T.;Li, Xingnan;Kuo, Calvin J.
通讯作者：
Kuo, Calvin J.