Highlights d Breast cancer cells treated with CDK4/6 inhibitor secrete chemokines CCL5 and CXCL10 d Chemokine induction is associated with deregulated mTOR, metabolic stress, and ROS d Chemokines induced by CDK4/6 inhibitor facilitate T cell infiltration into tumors d Chemokines induced by CDK4/6 inhibitor augment adoptive T cell therapy

Summary Patient-derived cancer organoids hold great potential to accurately model and predict therapeutic responses. Efficient organoid isolation methods that minimize post-collection manipulation of tissues would improve adaptability, accuracy, and applicability to both experimental and real-time clinical settings. Here we present a simple and minimally invasive fine-needle aspiration (FNA)-based organoid culture technique using a variety of tumor types including gastrointestinal, thyroid, melanoma, and kidney. This method isolates organoids directly from patients at the bedside or from resected tissues, requiring minimal tissue processing while preserving the histologic growth patterns and infiltrating immune cells. Finally, we illustrate diverse downstream applications of this technique including in vitro high-throughput chemotherapeutic screens, in situ immune cell characterization, and in vivo patient-derived xenografts. Thus, routine clinical FNA-based collection techniques represent an unappreciated substantial source of material that can be exploited to generate tumor organoids from a variety of tumor types for both discovery and clinical applications.

In experiments involving animals, the experiments were executed in compliance with institutional guidelines and regulations and after approval from the appropriate institutional review board (IACUC protocol number M1600236). The studies involving human tissue were conducted in accordance with the ethical principles and guidelines for research outlined in The Belmont Report (Vanderbilt IRB# M030220), and informed written consent was obtained from each subject or each subject's guardian.

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