Evidence map›Paper›PMID 36854570›Full record

Trial reportJournal for immunotherapy of cancer2023

Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody.

Xinyu Song, Anwen Xiong, Fengying Wu, Xuefei Li, Jing Wang, Tao Jiang, Peixin Chen, Xiaoshen Zhang, Zhikai Zhao, Huifang Liu and 8 more

Erratum issued Registry-linked trialOpen access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03838848 (A Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Patients With Advanced Non-small Cell Lung Cancer), which is not on this map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
13.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03838848 phase2terminatednot on this map

A Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Patients With Advanced Non-small Cell Lung Cancer

TypeinterventionalSponsorJiangsu Alphamab Biopharmaceuticals Co., LtdRan2019 to 2022Enrolled120ConditionsStage IV Non-small Cell Lung CancerArmsKN046, Carboplatin, Pemetrexed, Ningetinib
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Xinyu SongSchool of Medicine, Tongji University, Shanghai, China.ORCID 0000-0003-3158-8663
Anwen XiongDepartment of Medical Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Fengying WuDepartment of Medical Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Xuefei LiDepartment of Lung Cancer and Immunology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Jing WangClinical research center, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Tao JiangDepartment of Medical Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Peixin ChenSchool of Medicine, Tongji University, Shanghai, China.ORCID 0000-0002-4192-8396
Xiaoshen ZhangSchool of Medicine, Tongji University, Shanghai, China.
Zhikai ZhaoDepartment of Pathology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Huifang LiuDepartment of Pathology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Lei ChengDepartment of Lung Cancer and Immunology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Chao ZhaoDepartment of Lung Cancer and Immunology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Zhehai WangDepartment of Medical Oncology, Shandong Cancer Hospital, Jinan, Shandong, China.
Chaohu PanShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co Ltd, Shenzhen, Guangdong, China.
Xiaoli CuiShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co Ltd, Shenzhen, Guangdong, China.
Ting XuAlphamab Biopharmaceuticals, Suzhou, Jiangsu, China.
Haitao LuoShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co Ltd, Shenzhen, Guangdong, China caicunzhoudr@163.com luoht1985@gmail.com.
Caicun ZhouSchool of Medicine, Tongji University, Shanghai, China caicunzhoudr@163.com luoht1985@gmail.com.
Tongji University · CNShandong Tumor Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmunotherapy for malignant tumors has made great progress, but many patients do not benefit from it. The complex intratumoral heterogeneity (ITH) hindered the in-depth exploration of immunotherapy. Conventional bulk sequencing has masked intratumor complexity, preventing a more detailed discovery of the impact of ITH on treatment efficacy. Hence, we initiated this study to explore ITH at the multi-omics spatial level and to seek prognostic biomarkers of immunotherapy efficacy considering the presence of ITH.

methodsUsing the segmentation strategy of digital spatial profiling (DSP), we obtained differential information on tumor and stromal regions at the proteomic and transcriptomic levels. Based on the consideration of ITH, signatures constructed by candidate proteins in different regions were used to predict the efficacy of immunotherapy.

resultsEighteen patients treated with a bispecific antibody (bsAb)-KN046 were enrolled in this study. The tumor and stromal areas of the same samples exhibited distinct features. Signatures consisting of 11 and 18 differentially expressed DSP markers from the tumor and stromal areas, respectively, were associated with treatment response. Furthermore, the spatially resolved signature identified from the stromal areas showed greater predictive power for bsAb immunotherapy response (area under the curve=0.838). Subsequently, our stromal signature was validated in an independent cohort of patients with non-small cell lung cancer undergoing immunotherapy.

conclusionWe deciphered ITH at the spatial level and demonstrated for the first time that genetic information in the stromal region can better predict the efficacy of bsAb treatment. TRIAL REGISTRATION NUMBER: NCT03838848.

Indexed as

Antibodies, BispecificCarcinoma, Non-Small-Cell LungLung NeoplasmsEcosystemHumansImmunotherapyMultiomicsProteomicsAntibodies, Bispecificbiomarkers, tumorimmunotherapylung neoplasms

Identifiers

PMID36854570
PMCPMC9980352
OpenAlexW4322627262

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.