IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47301-9.html
   My bibliography  Save this article

Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma

Author

Listed:
  • Xinyu Bai

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Grace H. Attrill

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Tuba N. Gide

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Peter M. Ferguson

    (The University of Sydney
    The University of Sydney
    Royal Prince Alfred Hospital
    NSW Health Pathology)

  • Kazi J. Nahar

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ping Shang

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ismael A. Vergara

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Umaimainthan Palendira

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Ines Pires Silva

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Westmead and Blacktown Hospitals)

  • Matteo S. Carlino

    (The University of Sydney
    Westmead and Blacktown Hospitals)

  • Alexander M. Menzies

    (The University of Sydney
    The University of Sydney
    Royal North Shore Hospital
    Mater Hospital)

  • Georgina V. Long

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Royal North Shore Hospital)

  • Richard A. Scolyer

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Royal Prince Alfred Hospital)

  • James S. Wilmott

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Camelia Quek

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

Abstract

The biological underpinnings of therapeutic resistance to immune checkpoint inhibitors (ICI) in adolescent and young adult (AYA) melanoma patients are incompletely understood. Here, we characterize the immunogenomic profile and spatial architecture of the tumor microenvironment (TME) in AYA (aged ≤ 30 years) and older adult (aged 31–84 years) patients with melanoma, to determine the AYA-specific features associated with ICI treatment outcomes. We identify two ICI-resistant spatiotypes in AYA patients with melanoma showing stroma-infiltrating lymphocytes (SILs) that are distinct from the adult TME. The SILhigh subtype was enriched in regulatory T cells in the peritumoral space and showed upregulated expression of immune checkpoint molecules, while the SILlow subtype showed a lack of immune activation. We establish a young immunosuppressive melanoma score that can predict ICI responsiveness in AYA patients and propose personalized therapeutic strategies for the ICI-resistant subgroups. These findings highlight the distinct immunogenomic profile of AYA patients, and individualized TME features in ICI-resistant AYA melanoma that require patient-specific treatment strategies.

Suggested Citation

  • Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47301-9
    DOI: 10.1038/s41467-024-47301-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47301-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47301-9?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. 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.
    2. Nicholas K. Hayward & James S. Wilmott & Nicola Waddell & Peter A. Johansson & Matthew A. Field & Katia Nones & Ann-Marie Patch & Hojabr Kakavand & Ludmil B. Alexandrov & Hazel Burke & Valerie Jakrot , 2017. "Whole-genome landscapes of major melanoma subtypes," Nature, Nature, vol. 545(7653), pages 175-180, May.
    3. Andrea Castro & Rachel Marty Pyke & Xinlian Zhang & Wesley Kurt Thompson & Chi-Ping Day & Ludmil B. Alexandrov & Maurizio Zanetti & Hannah Carter, 2020. "Strength of immune selection in tumors varies with sex and age," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    4. Xiaojing Wang & Anne-Marie Langevin & Peter J. Houghton & Siyuan Zheng, 2022. "Genomic disparities between cancers in adolescent and young adults and in older adults," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Roy S. Herbst & Jean-Charles Soria & Marcin Kowanetz & Gregg D. Fine & Omid Hamid & Michael S. Gordon & Jeffery A. Sosman & David F. McDermott & John D. Powderly & Scott N. Gettinger & Holbrook E. K. , 2014. "Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients," Nature, Nature, vol. 515(7528), pages 563-567, November.
    6. Sara Akhavanfard & Roshan Padmanabhan & Lamis Yehia & Feixiong Cheng & Charis Eng, 2020. "Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    7. Jenny H. Lee & Elena Shklovskaya & Su Yin Lim & Matteo S. Carlino & Alexander M. Menzies & Ashleigh Stewart & Bernadette Pedersen & Malama Irvine & Sara Alavi & Jean Y. H. Yang & Dario Strbenac & Roby, 2020. "Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    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. Jing Liu & Xia Bu & Chen Chu & Xiaoming Dai & John M. Asara & Piotr Sicinski & Gordon J. Freeman & Wenyi Wei, 2023. "PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Su Yin Lim & Elena Shklovskaya & Jenny H. Lee & Bernadette Pedersen & Ashleigh Stewart & Zizhen Ming & Mal Irvine & Brindha Shivalingam & Robyn P. M. Saw & Alexander M. Menzies & Matteo S. Carlino & R, 2023. "The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Rachael M. Zemek & Wee Loong Chin & Vanessa S. Fear & Ben Wylie & Thomas H. Casey & Cath Forbes & Caitlin M. Tilsed & Louis Boon & Belinda B. Guo & Anthony Bosco & Alistair R. R. Forrest & Michael J. , 2022. "Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Hong Yuen Wong & Quanhu Sheng & Amanda B. Hesterberg & Sarah Croessmann & Brenda L. Rios & Khem Giri & Jorgen Jackson & Adam X. Miranda & Evan Watkins & Kerry R. Schaffer & Meredith Donahue & Elizabet, 2022. "Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    5. Mike B. Barnkob & Yale S. Michaels & Violaine André & Philip S. Macklin & Uzi Gileadi & Salvatore Valvo & Margarida Rei & Corinna Kulicke & Ji-Li Chen & Vitul Jain & Victoria K. Woodcock & Huw Colin-Y, 2024. "Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Brittany N. Vandenberg & Marian F. Laughery & Cameron Cordero & Dalton Plummer & Debra Mitchell & Jordan Kreyenhagen & Fatimah Albaqshi & Alexander J. Brown & Piotr A. Mieczkowski & John J. Wyrick & S, 2023. "Contributions of replicative and translesion DNA polymerases to mutagenic bypass of canonical and atypical UV photoproducts," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. 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.
    9. Anna Luiza Silva Almeida Vicente & Alexei Novoloaca & Vincent Cahais & Zainab Awada & Cyrille Cuenin & Natália Spitz & André Lopes Carvalho & Adriane Feijó Evangelista & Camila Souza Crovador & Rui Ma, 2022. "Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Guo Li & Saranya Srinivasan & Liwen Wang & Chaoyu Ma & Kai Guo & Wenhao Xiao & Wei Liao & Shruti Mishra & Xin Zhang & Yuanzheng Qiu & Qianjin Lu & Yong Liu & Nu Zhang, 2022. "TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. 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.
    12. Han Luo & Xuyang Xia & Li-Bin Huang & Hyunsu An & Minyuan Cao & Gyeong Dae Kim & Hai-Ning Chen & Wei-Han Zhang & Yang Shu & Xiangyu Kong & Zhixiang Ren & Pei-Heng Li & Yang Liu & Huairong Tang & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    13. Wei Cheng & Hao-Long Li & Shao-Yan Xi & Xiao-Feng Zhang & Yun Zhu & Le Xing & Yan-Xuan Mo & Mei-Mei Li & Fan-En Kong & Wen-Jie Zhu & Xiao-Gang Chen & Hui-Qing Cui & Zhi-Ming Cao & Yuan-Feng Gong & Yun, 2021. "Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    14. Kristian Bjørn Hessellund & Ganggang Xu & Yongtao Guan & Rasmus Waagepetersen, 2022. "Second‐order semi‐parametric inference for multivariate log Gaussian Cox processes," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 71(1), pages 244-268, January.
    15. Jingjie Yi & Omid Tavana & Huan Li & Donglai Wang & Richard J. Baer & Wei Gu, 2023. "Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Farshad Farshidfar & Kahn Rhrissorrakrai & Chaya Levovitz & Cong Peng & James Knight & Antonella Bacchiocchi & Juan Su & Mingzhu Yin & Mario Sznol & Stephan Ariyan & James Clune & Kelly Olino & Laxmi , 2022. "Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Martin Boström & Erik Larsson, 2022. "Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    18. Elaine Lai-Han Leung & Run-Ze Li & Xing-Xing Fan & Lily Yan Wang & Yan Wang & Zebo Jiang & Jumin Huang & Hu-Dan Pan & Yue Fan & Hongmei Xu & Feng Wang & Haopeng Rui & Piu Wong & Hermi Sumatoh & Michae, 2023. "Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    19. Jingjing Qi & Hongxiang Sun & Yao Zhang & Zhengting Wang & Zhenzhen Xun & Ziyi Li & Xinyu Ding & Rujuan Bao & Liwen Hong & Wenqing Jia & Fei Fang & Hongzhi Liu & Lei Chen & Jie Zhong & Duowu Zou & Lia, 2022. "Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    20. Wanzun Lin & Li Chen & Haojiong Zhang & Xianxin Qiu & Qingting Huang & Fangzhu Wan & Ziyu Le & Shikai Geng & Anlan Zhang & Sufang Qiu & Long Chen & Lin Kong & Jiade J. Lu, 2023. "Tumor-intrinsic YTHDF1 drives immune evasion and resistance to immune checkpoint inhibitors via promoting MHC-I degradation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

    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_s41467-024-47301-9. 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.