Appearance
Organoid Models of Tumor Immunology.
Literature Information
| DOI | 10.1016/j.it.2020.06.010 |
|---|---|
| PMID | 32654925 |
| Journal | Trends in immunology |
| Impact Factor | 13.9 |
| JCR Quartile | Q1 |
| Publication Year | 2020 |
| Times Cited | 217 |
| Keywords | immunotherapy, organoids, tumor microenvironment |
| Literature Type | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1471-4906 |
| Pages | 652-664 |
| Issue | 41(8) |
| Authors | Kanako Yuki, Ning Cheng, Michitaka Nakano, Calvin J Kuo |
TL;DR
This paper discusses the critical role of cellular interactions in the tumor microenvironment (TME) on cancer progression and treatment responses, highlighting the limitations of traditional 2D models in representing these interactions. It emphasizes the potential of innovative 3D organoid cultures using primary human tumor biopsies for advancing immuno-oncology research and enhancing the precision of immunotherapy approaches.
Search for more papers on MaltSci.com
immunotherapy · organoids · tumor microenvironment
Abstract
Cellular interactions in the tumor microenvironment (TME) significantly govern cancer progression and drug response. The efficacy of clinical immunotherapies has fostered an exponential interest in the tumor immune microenvironment, which in turn has engendered a pressing need for robust experimental systems modeling patient-specific tumor-immune interactions. Traditional 2D in vitro tumor immunotherapy models have reconstituted immortalized cancer cell lines with immune components, often from peripheral blood. However, newly developed 3D in vitro organoid culture methods now allow the routine culture of primary human tumor biopsies and increasingly incorporate immune components. Here, we present a viewpoint on recent advances, and propose translational applications of tumor organoids for immuno-oncology research, immunotherapy modeling, and precision medicine.
MaltSci.com AI Research Service
Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining
Primary Questions Addressed
- How do organoid models compare to traditional 2D models in terms of mimicking the tumor microenvironment?
- What specific immune components can be incorporated into organoid cultures to enhance their relevance for immunotherapy research?
- In what ways can organoid models facilitate the development of personalized immunotherapy strategies for cancer patients?
- What are the limitations of current organoid models in accurately representing the complexities of tumor-immune interactions?
- How might advancements in organoid technology impact future clinical trials for immunotherapies?
Key Findings
Research Background and Purpose
The study focuses on the development and application of organoid models to better understand tumor immunology and the tumor microenvironment (TME). Traditional 2D and animal models have limitations in replicating the complex interactions between tumor cells and the immune system. The authors highlight the need for advanced experimental systems that can model patient-specific tumor-immune interactions to enhance immunotherapy research and precision medicine.
Main Methods/Materials/Experimental Design
The authors present various organoid culture systems to model the TME, including:
Submerged Matrigel Culture: Tumor cells are cultured in a 3D Matrigel matrix with added growth factors to support self-renewal and differentiation. This method typically lacks stromal components and requires co-culture with immune cells for TME modeling.
Microfluidic 3D Culture: This system allows for the growth of tumor spheroids in a 3D gel with parallel media channels, preserving autologous immune cells and tumor cells.
Air-Liquid Interface (ALI) Culture: Tumor organoids are embedded in collagen gel with an exposed top layer to air, promoting oxygen access and retaining both tumor and immune components from the original tissue.
Key Results and Findings
- Organoid models successfully replicate the genetic and phenotypic diversity of tumors, providing a more accurate representation of patient tumors compared to traditional models.
- The ALI culture method retains the complexity of the TME, including diverse immune cell populations and stromal components.
- Tumor organoids can effectively model responses to immune checkpoint inhibitors (ICIs) and adoptive cell therapies (ACTs), revealing the potential for personalized cancer immunotherapy.
Main Conclusions/Significance/Innovation
The integration of immune components into organoid models represents a significant advancement in cancer research. These models allow for the investigation of tumor-immune interactions, the testing of immunotherapeutics, and the development of personalized treatment strategies. The study emphasizes the importance of creating holistic models that accurately reflect the native TME, which can enhance our understanding of immunotherapy responses and resistance mechanisms.
Research Limitations and Future Directions
- The study acknowledges challenges in maintaining immune cell viability and function over extended culture periods, which limits long-term studies.
- Future research should focus on optimizing culture conditions to enhance immune cell preservation and exploring the interactions between tumor cells and various immune populations in more complex models.
- The authors suggest that organoid models can be further developed to investigate cancer-associated inflammation and pathogen interactions, which could lead to novel therapeutic insights.
Summary Table of Organoid Culture Systems
| Feature | Submerged Matrigel Culture | Microfluidic 3D Culture | ALI Culture |
|---|---|---|---|
| Source | Patient-derived and mouse-derived tumors | Patient and murine tumors | Primary human biopsies |
| Retained Components | Tumor cells only; lacks immune/stromal cells | Tumor cells and some immune cells | Tumor cells, native immune cells, and stroma |
| Culture Duration | Long-term for organoid expansion | Short-term; long-term not reported | Long-term for tumor cells; immune cells decline |
| Advantages | Easy to expand; models tumor diversity | Preserves multiple cell types; small sample | Preserves immune components; models interactions |
| Limitations | Lacks native immune and stromal components | Requires specialized equipment; size limits | Immune components decline over time |
This structured summary encapsulates the core findings and methodologies of the study, highlighting the potential of organoid models in advancing cancer immunotherapy research.
References
- HTiP: High-Throughput Immunomodulator Phenotypic Screening Platform to Reveal IAP Antagonists as Anti-cancer Immune Enhancers. - Xiulei Mo;Cong Tang;Qiankun Niu;Tingxuan Ma;Yuhong Du;Haian Fu - Cell chemical biology (2019)
- Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer. - Jayati Chakrabarti;Loryn Holokai;LiJyun Syu;Nina G Steele;Julie Chang;Jiang Wang;Syed Ahmed;Andrzej Dlugosz;Yana Zavros - Oncotarget (2018)
- PD-1 blockade induces responses by inhibiting adaptive immune resistance. - Paul C Tumeh;Christina L Harview;Jennifer H Yearley;I Peter Shintaku;Emma J M Taylor;Lidia Robert;Bartosz Chmielowski;Marko Spasic;Gina Henry;Voicu Ciobanu;Alisha N West;Manuel Carmona;Christine Kivork;Elizabeth Seja;Grace Cherry;Antonio J Gutierrez;Tristan R Grogan;Christine Mateus;Gorana Tomasic;John A Glaspy;Ryan O Emerson;Harlan Robins;Robert H Pierce;David A Elashoff;Caroline Robert;Antoni Ribas - Nature (2014)
- A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening. - Helen H N Yan;Hoi Cheong Siu;Simon Law;Siu Lun Ho;Sarah S K Yue;Wai Yin Tsui;Dessy Chan;April S Chan;Stephanie Ma;Ka On Lam;Sina Bartfeld;Alice H Y Man;Bernard C H Lee;Annie S Y Chan;Jason W H Wong;Priscilla S W Cheng;Anthony K W Chan;Jiangwen Zhang;Jue Shi;Xiaodan Fan;Dora L W Kwong;Tak W Mak;Siu Tsan Yuen;Hans Clevers;Suet Yi Leung - Cell stem cell (2018)
- Adoptive T Cell Therapy: New Avenues Leading to Safe Targets and Powerful Allies. - Dora Hammerl;Dietmar Rieder;John W M Martens;Zlatko Trajanoski;Reno Debets - Trends in immunology (2018)
- Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. - Padmanee Sharma;Siwen Hu-Lieskovan;Jennifer A Wargo;Antoni Ribas - Cell (2017)
- TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. - Sanjeev Mariathasan;Shannon J Turley;Dorothee Nickles;Alessandra Castiglioni;Kobe Yuen;Yulei Wang;Edward E Kadel;Hartmut Koeppen;Jillian L Astarita;Rafael Cubas;Suchit Jhunjhunwala;Romain Banchereau;Yagai Yang;Yinghui Guan;Cecile Chalouni;James Ziai;Yasin Şenbabaoğlu;Stephen Santoro;Daniel Sheinson;Jeffrey Hung;Jennifer M Giltnane;Andrew A Pierce;Kathryn Mesh;Steve Lianoglou;Johannes Riegler;Richard A D Carano;Pontus Eriksson;Mattias Höglund;Loan Somarriba;Daniel L Halligan;Michiel S van der Heijden;Yohann Loriot;Jonathan E Rosenberg;Lawrence Fong;Ira Mellman;Daniel S Chen;Marjorie Green;Christina Derleth;Gregg D Fine;Priti S Hegde;Richard Bourgon;Thomas Powles - Nature (2018)
- Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. - Mark A Socinski;Robert M Jotte;Federico Cappuzzo;Francisco Orlandi;Daniil Stroyakovskiy;Naoyuki Nogami;Delvys Rodríguez-Abreu;Denis Moro-Sibilot;Christian A Thomas;Fabrice Barlesi;Gene Finley;Claudia Kelsch;Anthony Lee;Shelley Coleman;Yu Deng;Yijing Shen;Marcin Kowanetz;Ariel Lopez-Chavez;Alan Sandler;Martin Reck; - The New England journal of medicine (2018)
- Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. - Robert J Motzer;Bernard Escudier;David F McDermott;Saby George;Hans J Hammers;Sandhya Srinivas;Scott S Tykodi;Jeffrey A Sosman;Giuseppe Procopio;Elizabeth R Plimack;Daniel Castellano;Toni K Choueiri;Howard Gurney;Frede Donskov;Petri Bono;John Wagstaff;Thomas C Gauler;Takeshi Ueda;Yoshihiko Tomita;Fabio A Schutz;Christian Kollmannsberger;James Larkin;Alain Ravaud;Jason S Simon;Li-An Xu;Ian M Waxman;Padmanee Sharma; - The New England journal of medicine (2015)
- Modelling cancer in microfluidic human organs-on-chips. - Alexandra Sontheimer-Phelps;Bryan A Hassell;Donald E Ingber - Nature reviews. Cancer (2019)
Literatures Citing This Work
- Targeting TANK-binding kinase 1 (TBK1) in cancer. - Or-Yam Revach;Shuming Liu;Russell W Jenkins - Expert opinion on therapeutic targets (2020)
- Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice. - Hui-Ching Wang;Tsung-Jang Yeh;Leong-Perng Chan;Chin-Mu Hsu;Shih-Feng Cho - International journal of molecular sciences (2020)
- The future of microfluidics in immune checkpoint blockade. - Jonathan Briones;Wilfred Espulgar;Shohei Koyama;Hyota Takamatsu;Eiichi Tamiya;Masato Saito - Cancer gene therapy (2021)
- Targeting metastatic cancer. - Karuna Ganesh;Joan Massagué - Nature medicine (2021)
- Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models. - P Jonathan Li;Jeroen P Roose;David M Jablons;Johannes R Kratz - Cancers (2021)
- An expanded universe of cancer targets. - William C Hahn;Joel S Bader;Theodore P Braun;Andrea Califano;Paul A Clemons;Brian J Druker;Andrew J Ewald;Haian Fu;Subhashini Jagu;Christopher J Kemp;William Kim;Calvin J Kuo;Michael McManus;Gordon B Mills;Xiulei Mo;Nidhi Sahni;Stuart L Schreiber;Jessica A Talamas;Pablo Tamayo;Jeffrey W Tyner;Bridget K Wagner;William A Weiss;Daniela S Gerhard; - Cell (2021)
- Patient-Derived Organoids for Precision Cancer Immunotherapy. - Mikaela Grönholm;Michaela Feodoroff;Gabriella Antignani;Beatriz Martins;Firas Hamdan;Vincenzo Cerullo - Cancer research (2021)
- Recent advances in preclinical models for lung squamous cell carcinoma. - Yuanwang Pan;Han Han;Kristen E Labbe;Hua Zhang;Kwok-Kin Wong - Oncogene (2021)
- The Role of Network Science in Glioblastoma. - Marta B Lopes;Eduarda P Martins;Susana Vinga;Bruno M Costa - Cancers (2021)
- Patient-Derived Organoids as a Model for Cancer Drug Discovery. - Colin Rae;Francesco Amato;Chiara Braconi - International journal of molecular sciences (2021)
... (207 more literatures)
© 2025 MaltSci - We reshape scientific research with AI technology