IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53197-2.html
   My bibliography  Save this article

68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial

Author

Listed:
  • Xiuling Shen

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Haoyi Zhou

    (Peking University Health Science Center)

  • Xin Zhou

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Zongchao Liu

    (Peking University Cancer Hospital & Institute)

  • Xiangxi Meng

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Linyu Zhang

    (Peking University Health Science Center)

  • Yufei Song

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Rui Guo

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Fei Wang

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Kui Li

    (Peking University Health Science Center)

  • Wenqing Li

    (Peking University Cancer Hospital & Institute)

  • Zhi Yang

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Zhaofei Liu

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute
    Peking University Health Science Center
    Peking University Third Hospital)

  • Nan Li

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

Abstract

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Suggested Citation

  • Xiuling Shen & Haoyi Zhou & Xin Zhou & Zongchao Liu & Xiangxi Meng & Linyu Zhang & Yufei Song & Rui Guo & Fei Wang & Kui Li & Wenqing Li & Zhi Yang & Zhaofei Liu & Nan Li, 2024. "68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53197-2
    DOI: 10.1038/s41467-024-53197-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53197-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-53197-2?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. Yannick Simoni & Etienne Becht & Michael Fehlings & Chiew Yee Loh & Si-Lin Koo & Karen Wei Weng Teng & Joe Poh Sheng Yeong & Rahul Nahar & Tong Zhang & Hassen Kared & Kaibo Duan & Nicholas Ang & Micha, 2018. "Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates," Nature, Nature, vol. 557(7706), pages 575-579, May.
    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.
    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. Hong Sheng Quah & Elaine Yiqun Cao & Lisda Suteja & Constance H. Li & Hui Sun Leong & Fui Teen Chong & Shilpi Gupta & Camille Arcinas & John F. Ouyang & Vivian Ang & Teja Celhar & Yunqian Zhao & Hui C, 2023. "Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. 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.
    3. 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.
    4. Irma Telarovic & Carmen S. M. Yong & Lisa Kurz & Irene Vetrugno & Sabrina Reichl & Alba Sanchez Fernandez & Hung-Wei Cheng & Rona Winkler & Matthias Guckenberger & Anja Kipar & Burkhard Ludewig & Mart, 2024. "Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    5. 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.
    6. 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.
    7. 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.
    8. Marina Baretti & Ludmila Danilova & Jennifer N. Durham & Courtney B. Betts & Leslie Cope & Dimitrios N. Sidiropoulos & Joseph A. Tandurella & Soren Charmsaz & Nicole Gross & Alexei Hernandez & Won Jin, 2024. "Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. 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.
    10. 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.
    11. 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.
    12. Zhenlin Yang & He Tian & Xiaowei Chen & Bozhao Li & Guangyu Bai & Qingyuan Cai & Jiachen Xu & Wei Guo & Shuaibo Wang & Yue Peng & Qing Liang & Liyan Xue & Shugeng Gao, 2024. "Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Judit Svensson-Arvelund & Sara Cuadrado-Castano & Gvantsa Pantsulaia & Kristy Kim & Mark Aleynick & Linda Hammerich & Ranjan Upadhyay & Michael Yellin & Henry Marsh & Daniel Oreper & Suchit Jhunjhunwa, 2022. "Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. 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.
    15. Jani Huuhtanen & Liang Chen & Emmi Jokinen & Henna Kasanen & Tapio Lönnberg & Anna Kreutzman & Katriina Peltola & Micaela Hernberg & Chunlin Wang & Cassian Yee & Harri Lähdesmäki & Mark M. Davis & Sat, 2022. "Evolution and modulation of antigen-specific T cell responses in melanoma patients," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. Lianmei Tan & Tao Yin & Handan Xiang & Liuyang Wang & Poorva Mudgal & Junying Chen & Yi Ding & Guoping Wang & Bryan Jian Wei Lim & Yuqi Huang & De Huang & Yaosi Liang & Peter B. Alexander & Kun Xiang , 2024. "Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. 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.
    18. Sakina A. Plumber & Tiffany Tate & Hikmat Al-Ahmadie & Xiao Chen & Woonyoung Choi & Merve Basar & Chao Lu & Aaron Viny & Ekatherina Batourina & Jiaqi Li & Kristjan Gretarsson & Besmira Alija & Andrei , 2024. "Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Maud Rijnders & J. Alberto Nakauma-González & Debbie G. J. Robbrecht & Alberto Gil-Jimenez & Hayri E. Balcioglu & Astrid A. M. Oostvogels & Maureen J. B. Aarts & Joost L. Boormans & Paul Hamberg & Mic, 2024. "Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in urothelial cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    20. Hanhan Ning & Shan Huang & Yang Lei & Renyong Zhi & Han Yan & Jiaxing Jin & Zhenyu Hu & Kaimin Guo & Jinhua Liu & Jie Yang & Zhe Liu & Yi Ba & Xin Gao & Deqing Hu, 2022. "Enhancer decommissioning by MLL4 ablation elicits dsRNA-interferon signaling and GSDMD-mediated pyroptosis to potentiate anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-20, 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_s41467-024-53197-2. 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.