ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.
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Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 39 citations in OpenAlex.
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- Circulating proteins as biomarkers of response to cancer immunotherapy (Review).International journal of oncology · 2026Review
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- The Proteo-Transcriptome of Extracellular Vesicles and Particles Is Largely Preserved After Cryopreservation.Journal of extracellular biology · 2026Article
- Multimodal approach for the comprehensive management of non-small cell lung cancer: a case report.Translational cancer research · 2026Article
- Targeting cell membrane sphingolipids: a novel ceramide analog CeY-B1 inhibits migration and invasion in cervical cancer cells.Journal of translational medicine · 2026Article
- Comprehensive multi omics profiling and Mendelian randomization assessment of lipid metabolites in lung cancer prognosis.Discover oncology · 2026Article
- Effectiveness and safety of combination immunotherapy with or without ipilimumab according to PD-L1 expression in patients with non-small cell lung cancer: a multi-center retrospective cohort study.Translational lung cancer research · 2026Article
- Higher proximity of PD-L1Translational lung cancer research · 2026Article
- Integrative multiomic profiling of cfDNA methylation and EV-miRNAs identifies immunotherapy-outcome molecular subtypes in NSCLC.Journal for immunotherapy of cancer · 2026Article
- Integrating chemokine signatures and multi-omic biomarkers to predict immunotherapy response in non-small cell lung cancer: a comprehensive narrative review.Frontiers in oncology · 2026Review
- Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.ImmunoTargets and therapy · 2026Review
- Mapping the rapid growth of multi-omics in tumor immunotherapy: Bibliometric evidence of technology convergence and paradigm shifts.Human vaccines & immunotherapeutics · 2025Article
- Interpretable machine learning model integrating CT radiomics, CTR, and clinical features for EGFR mutation prediction in ≤3 cm lung adenocarcinoma nodules.Annals of medicine · 2025Article
- T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma.Oncology reports · 2025Article
- Narciclasine as a Novel Treatment for Lung Cancer and Malignant Pleural Mesothelioma: Insights from 3D Tumor Spheroid Models.International journal of molecular sciences · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- A comprehensive analysis through Mendelian randomization of immunological markers and sphingolipid metabolism.Discover oncology · 2025Article
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Authors and funding
47 authors at 9 institutions in 1 country.
Edwin Roger Parra *Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9068-1636
Jiexin Zhang *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9526-6730
Dzifa Yawa Duose *Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6763-9736
Edgar Gonzalez-Kozlova *Department of Oncological Sciences, Mount Sinai, New York, New York.ORCID 0000-0002-6948-0626
Mary W RedmanSWOG Statistical Center, Fred Hutchinson Cancer Center, Seattle, Washington.ORCID 0000-0003-2294-9674
Hong ChenDepartment of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-8054-7417
Ganiraju C ManyamDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-6006-8961
Gayatri KumarDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-3686-5471
Jianhua ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-5412-9860
Xingzhi SongDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-9436-2728
Rossana LazcanoDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9890-2325
Mario L Marques-PiubelliDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6324-2096
Caddie Laberiano-FernandezDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-4513-6123
Frank RojasDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-2605-435X
Baili ZhangDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0005-4024-5840
Len TaingCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-7453-5372
Aashna JhaveriCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0002-6609-8306
Jacob GeisbergCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0009-5786-9771
Jennifer AltreuterCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6545-6496
Franziska MichorCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-4869-8842
James ProvencherCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0002-1993-3065
Joyce YuCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0000-4811-2747
Ethan CeramiCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0009-2340-4490
Radim MoravecCancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, NCI, Bethesda, Maryland.ORCID 0009-0005-5837-7315
Kasthuri KannanDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-6993-5141
Rajyalakshmi LuthraDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-7133-0221
Gheath AlatrashDepartment of Stem Cell Transplantation, The University of Texas MD Anderson Cancer, Houston, Texas.ORCID 0000-0002-7648-4377
Hsin-Hui HuangPrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0000-0001-7160-5179
Hui XiePrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0009-0003-3532-7150
Manishkumar PatelPrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0000-0002-7949-5610
Kai NiePrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0000-0002-8253-9688
Jocelyn HarrisPrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0000-0003-4289-8544
Kimberly ArguetaPrecision Immunology Institute, Mount Sinai, New York, New York.ORCID 0009-0002-3102-8869
James LindsayDepartment of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-6295-098X
Roshni BiswasDepartment of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-3917-5145
Stephen Van NostrandCIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0003-6083-6272
Seunghee Kim-SchulzeDepartment of Oncological Sciences, Mount Sinai, New York, New York.ORCID 0000-0003-0192-4400
Jhanelle E GrayMoffitt Cancer Caner, Tampa, Florida.ORCID 0000-0003-1304-7062
Roy S HerbstYale Cancer Center, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0003-2535-5847
Ignacio I WistubaDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-3365-6340
Scott GettingerMoffitt Cancer Caner, Tampa, Florida.ORCID 0000-0003-0886-6880
Karen KellyInternational Association for the Study of Lung Cancer, Denver, Colorado.ORCID 0000-0002-2235-6636
Lyudmila BazhenovaUniversity of California San Diego Moores Cancer Center, La Jolla, California.ORCID 0000-0001-8764-4359
Sacha GnjaticDepartment of Oncological Sciences, Mount Sinai, New York, New York.ORCID 0000-0001-5643-9520
J Jack LeeDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-5469-9214
Jianjun ZhangDepartment of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-7872-3477
Cara HaymakerDepartments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-1317-9287
The University of Texas MD Anderson Cancer Center · USDana-Farber Cancer Institute · USMount Sinai Hospital · USMoffitt Cancer Center · USCenter for Cancer Research · USFred Hutch Cancer Center · USInternational Association for the Study of Lung Cancer · USUniversity of California San Diego · USYale Cancer Center · US
Funding
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1MSWOG Statistics & Data Management Center complex - extension supplement for GY06U10CA180819 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MEGAN OTHUS · 2014 to 2026
$115.2MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MConduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4MTHE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4MHigh-Dimensional Immune Monitoring of NCI-Supported Immunotherapy TrialsU24CA224319 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Sacha Gnjatic, Seunghee Kim-Schulze · 2017 to 2026
$21.5MTranslational Cancer Immune Monitoring and Analysis Center (TCIMAC)U24CA224285 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gheath Al-Atrash, Cara L Haymaker · 2017 to 2026
$16.7MCancer Immunologic Data Commons (CIDC) Supplement RequestU24CA224316 · NCI · DANA-FARBER CANCER INST · PI CERAMI, ETHAN, MICHOR, FRANZISKA · 2017 to 2022
$6.8MCharacterizing and predicting colitis in immune checkpoint blockade-treated cancer patientsU01DK124165 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI COLOMBEL, JEAN-FREDERIC, FAITH, JEREMIAH JAMES · 2020 to 2024
$2.9MPRIMAVO: Interactive exploration of cancer patient precision immune monitoring data in clinical trialsR33CA263705 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GUMUS, ZEYNEP HULYA · 2021 to 2021
$1.5MNCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR004419NCI NIH HHS P30 CA196521NCI NIH HHS R33 CA263705NCI NIH HHS U10 CA180819NCI NIH HHS U10 CA180888NCI NIH HHS U24 CA224285NCI NIH HHS U24 CA224316NCI NIH HHS U24 CA224319NIDDK NIH HHS U01 DK124165
Abstract
purposeIdentifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL
designTissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink.
resultsHigher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression.
conclusionsThe frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.
Indexed as
Carcinoma, Non-Small-Cell LungCarcinoma, Squamous CellLung NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsEpithelial CellsHumansImmunotherapyIpilimumabLungMultiomicsNivolumabTumor MicroenvironmentIpilimumabNivolumab
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