IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46450-1.html
   My bibliography  Save this article

Spatial relationships in the urothelial and head and neck tumor microenvironment predict response to combination immune checkpoint inhibitors

Author

Listed:
  • Alberto Gil-Jimenez

    (The Netherlands Cancer Institute
    Oncode Institute)

  • Nick Dijk

    (The Netherlands Cancer Institute)

  • Joris L. Vos

    (The Netherlands Cancer Institute
    The Netherlands Cancer Institute)

  • Yoni Lubeck

    (The Netherlands Cancer Institute)

  • Maurits L. Montfoort

    (The Netherlands Cancer Institute)

  • Dennis Peters

    (Netherlands Cancer Institute)

  • Erik Hooijberg

    (The Netherlands Cancer Institute)

  • Annegien Broeks

    (Netherlands Cancer Institute)

  • Charlotte L. Zuur

    (The Netherlands Cancer Institute
    The Netherlands Cancer Institute
    Department of Otorhinolaryngology Head and Neck Surgery)

  • Bas W. G. Rhijn

    (The Netherlands Cancer Institute
    University of Regensburg)

  • Daniel J. Vis

    (The Netherlands Cancer Institute
    Oncode Institute)

  • Michiel S. Heijden

    (The Netherlands Cancer Institute
    The Netherlands Cancer Institute)

  • Lodewyk F. A. Wessels

    (The Netherlands Cancer Institute
    Oncode Institute
    Delft University of Technology)

Abstract

Immune checkpoint inhibitors (ICI) can achieve remarkable responses in urothelial cancer (UC), which may depend on tumor microenvironment (TME) characteristics. However, the relationship between the TME, usually characterized by immune cell density, and response to ICI is unclear. Here, we quantify the TME immune cell densities and spatial relationships (SRs) of 24 baseline UC samples, obtained before pre-operative combination ICI treatment, using multiplex immunofluorescence. We describe SRs by approximating the first nearest-neighbor distance distribution with a Weibull distribution and evaluate the association between TME metrics and ipilimumab+nivolumab response. Immune cell density does not discriminate between response groups. However, the Weibull SR metrics of CD8+ T cells or macrophages to their closest cancer cell positively associate with response. CD8+ T cells close to B cells are characteristic of non-response. We validate our SR response associations in a combination ICI cohort of head and neck tumors. Our data confirm that SRs, in contrast to density metrics, are strong biomarkers of response to pre-operative combination ICIs.

Suggested Citation

  • Alberto Gil-Jimenez & Nick Dijk & Joris L. Vos & Yoni Lubeck & Maurits L. Montfoort & Dennis Peters & Erik Hooijberg & Annegien Broeks & Charlotte L. Zuur & Bas W. G. Rhijn & Daniel J. Vis & Michiel S, 2024. "Spatial relationships in the urothelial and head and neck tumor microenvironment predict response to combination immune checkpoint inhibitors," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46450-1
    DOI: 10.1038/s41467-024-46450-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46450-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-46450-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    2. Sanjeev Mariathasan & Shannon J. Turley & Dorothee Nickles & Alessandra Castiglioni & Kobe Yuen & Yulei Wang & Edward E. Kadel III & Hartmut Koeppen & Jillian L. Astarita & Rafael Cubas & Suchit Jhunj, 2018. "TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells," Nature, Nature, vol. 554(7693), pages 544-548, February.
    3. Joris L. Vos & Joris B. W. Elbers & Oscar Krijgsman & Joleen J. H. Traets & Xiaohang Qiao & Anne M. Leun & Yoni Lubeck & Iris M. Seignette & Laura A. Smit & Stefan M. Willems & Michiel W. M. Brekel & , 2021. "Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Daniel S. Chen & Ira Mellman, 2017. "Elements of cancer immunity and the cancer–immune set point," Nature, Nature, vol. 541(7637), pages 321-330, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Mengxue Zhou & Jiaxin Wang & Jiaxing Pan & Hui Wang & Lujia Huang & Bo Hou & Yi Lai & Fengyang Wang & Qingxiang Guan & Feng Wang & Zhiai Xu & Haijun Yu, 2023. "Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Darci Phillips & Magdalena Matusiak & Belén Rivero Gutierrez & Salil S. Bhate & Graham L. Barlow & Sizun Jiang & Janos Demeter & Kimberly S. Smythe & Robert H. Pierce & Steven P. Fling & Nirasha Ramch, 2021. "Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. Feng Xie & Xiaoxue Zhou & Peng Su & Heyu Li & Yifei Tu & Jinjin Du & Chen Pan & Xiang Wei & Min Zheng & Ke Jin & Liyan Miao & Chao Wang & Xuli Meng & Hans Dam & Peter Dijke & Long Zhang & Fangfang Zho, 2022. "Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-β type II receptor signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Alessandra Castiglioni & Yagai Yang & Katherine Williams & Alvin Gogineni & Ryan S. Lane & Amber W. Wang & Justin A. Shyer & Zhe Zhang & Stephanie Mittman & Alan Gutierrez & Jillian L. Astarita & Minh, 2023. "Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Fotis Nikolos & Kazukuni Hayashi & Xen Ping Hoi & Mark Ellie Alonzo & Qianxing Mo & Armine Kasabyan & Hideki Furuya & Jane Trepel & Dolores Vizio & Jlenia Guarnerio & Dan Theodorescu & Charles Rosser , 2022. "Cell death-induced immunogenicity enhances chemoimmunotherapeutic response by converting immune-excluded into T-cell inflamed bladder tumors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. JANSSENS, Jochen & DE CORTE, Annelies & SÖRENSEN, Kenneth, 2016. "Water distribution network design optimisation with respect to reliability," Working Papers 2016007, University of Antwerp, Faculty of Business and Economics.
    7. Raymond Hernandez & Elizabeth A. Pyatak & Cheryl L. P. Vigen & Haomiao Jin & Stefan Schneider & Donna Spruijt-Metz & Shawn C. Roll, 2021. "Understanding Worker Well-Being Relative to High-Workload and Recovery Activities across a Whole Day: Pilot Testing an Ecological Momentary Assessment Technique," IJERPH, MDPI, vol. 18(19), pages 1-17, October.
    8. Elisabeth Beckmann & Lukas Olbrich & Joseph Sakshaug, 2024. "Multivariate assessment of interviewer-related errors in a cross-national economic survey (Lukas Olbrich, Elisabeth Beckmann, Joseph W. Sakshaug)," Working Papers 253, Oesterreichische Nationalbank (Austrian Central Bank).
    9. Valentina Krenz & Arjen Alink & Tobias Sommer & Benno Roozendaal & Lars Schwabe, 2023. "Time-dependent memory transformation in hippocampus and neocortex is semantic in nature," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Morán-Ordóñez, Alejandra & Ameztegui, Aitor & De Cáceres, Miquel & de-Miguel, Sergio & Lefèvre, François & Brotons, Lluís & Coll, Lluís, 2020. "Future trade-offs and synergies among ecosystem services in Mediterranean forests under global change scenarios," Ecosystem Services, Elsevier, vol. 45(C).
    11. Damian M. Herz & Manuel Bange & Gabriel Gonzalez-Escamilla & Miriam Auer & Keyoumars Ashkan & Petra Fischer & Huiling Tan & Rafal Bogacz & Muthuraman Muthuraman & Sergiu Groppa & Peter Brown, 2022. "Dynamic control of decision and movement speed in the human basal ganglia," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Dongyan Liu & Chongran Zhou & John K. Keesing & Oscar Serrano & Axel Werner & Yin Fang & Yingjun Chen & Pere Masque & Janine Kinloch & Aleksey Sadekov & Yan Du, 2022. "Wildfires enhance phytoplankton production in tropical oceans," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    14. Zhaogeng Yang & Yanhui Li & Peijin Hu & Jun Ma & Yi Song, 2020. "Prevalence of Anemia and its Associated Factors among Chinese 9-, 12-, and 14-Year-Old Children: Results from 2014 Chinese National Survey on Students Constitution and Health," IJERPH, MDPI, vol. 17(5), pages 1-10, February.
    15. Aditi Sahu & Kivanc Kose & Lukas Kraehenbuehl & Candice Byers & Aliya Holland & Teguru Tembo & Anthony Santella & Anabel Alfonso & Madison Li & Miguel Cordova & Melissa Gill & Christi Fox & Salvador G, 2022. "In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Marco Lopez-Cruz & Fernando M. Aguate & Jacob D. Washburn & Natalia Leon & Shawn M. Kaeppler & Dayane Cristina Lima & Ruijuan Tan & Addie Thompson & Laurence Willard Bretonne & Gustavo los Campos, 2023. "Leveraging data from the Genomes-to-Fields Initiative to investigate genotype-by-environment interactions in maize in North America," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Baumann, Elias & Kern, Jana & Lessmann, Stefan, 2019. "Usage Continuance in Software-as-a-Service," IRTG 1792 Discussion Papers 2019-005, Humboldt University of Berlin, International Research Training Group 1792 "High Dimensional Nonstationary Time Series".
    18. repec:cup:judgdm:v:16:y:2021:i:1:p:201-237 is not listed on IDEAS
    19. C. Gabriel Hidalgo Pizango & Eurídice N. Honorio Coronado & Jhon del Águila-Pasquel & Gerardo Flores Llampazo & Johan de Jong & César J. Córdova Oroche & José M. Reyna Huaymacari & Steve J. Carver & D, 2022. "Sustainable palm fruit harvesting as a pathway to conserve Amazon peatland forests," Nature Sustainability, Nature, vol. 5(6), pages 479-487, June.
    20. Szefer Elena & Lu Donghuan & Nathoo Farouk & Beg Mirza Faisal & Graham Jinko, 2017. "Multivariate association between single-nucleotide polymorphisms in Alzgene linkage regions and structural changes in the brain: discovery, refinement and validation," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 16(5-6), pages 367-386, December.
    21. Julien Collet & Samantha C Patrick & Henri Weimerskirch, 2017. "A comparative analysis of the behavioral response to fishing boats in two albatross species," Behavioral Ecology, International Society for Behavioral Ecology, vol. 28(5), pages 1337-1347.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46450-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.