ArticleScience (New York, N.Y.)2015
Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.
13 registry-linked trialsAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 13 registered trials, which are not on this map. Cited by 4,877 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
4,877citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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.
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.
Identifying Genetic Predictors of Durable Clinical Benefit to Pembrolizumab in Advanced Non-small Cell Lung Cancer (NSCLC) Alone and in Combination With Chemotherapy.
Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis
A Randomized Phase II Study Evaluating Pembrolizumab vs Topotecan in the Second-Line Treatment of Patients With Small Cell Lung Cancer
A Phase 2 Study of Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination With Capecitabine and Oxaliplatin (CAPOX) in Subjects With Advanced Biliary Tract Carcinoma (BTC)
A Phase II, Open Label, Single Arm Study of Nivolumab for Recurrent or Progressive IDH Mutant Gliomas With Prior Exposure to Alkylating Agents
An Exploratory Study of Nivolumab With or Without Ipilimumab According to the Percentage of Tumoral CD8 Cells in Participants With Advanced Metastatic Cancer
An Open Label, Non-Randomized Multisite Phase II Trial Combining Bevacizumab, Atezolizumab and Rucaparib for the Treatment of Previously Treated Recurrent and Progressive Endometrial Carcinoma
NCT03918252 phase2active not recruitingnot on this mapstarted 2019, after this paper: background citation
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma
A Phase II, Single Arm Study of CarbopLatin Plus Etoposide With Bevacizumab and Atezolizumab in Patients With exTEnded-disease Small-cell Lung Cancer (SCLC)
A Phase II Study of Nivolumab in Patients With Genetic Alterations in DNA Damage Repair and Response Who Progressed After Standard Treatment for Metastatic Solid Cancers
Prospective Translational Study Investigating Predictors of Outcome in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab (I-Rene Trial)
A Study on Serum Exosomal miRNA Predicting the Effective and Prognosis of Immunotherapy Combined With Chemotherapy in Pulmonary Squamous Carcinoma
NCT07281716 phase1 / phase2recruitingnot on this mapstarted 2025, after this paper: background citation
A Phase 1b/2 Study of Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)
Who cites it
4,877 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- First-Line Immunotherapy Versus Chemotherapy in MSI-H/dMMR Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis of Phase III Studies.Journal of gastrointestinal cancer · 2026Pooled it
- Immune checkpoint inhibitor therapy for treatment of periocular Merkel cell carcinoma: A systematic review of clinical outcomes and safety.Indian journal of ophthalmology · 2026Pooled it
- Efficacy of PD-1/PD-L1 plus CTLA-4 inhibitors in advanced/metastatic NSCLC: a meta-analysis based on RCTs.Frontiers in immunology · 2026Pooled it
- Efficacy of first-line immune checkpoint inhibitors in advanced non-small-cell lung cancer with or without brain metastases: a systematic review and network meta-analysis.Frontiers in oncology · 2026Pooled it
- Targeting DNA damage response to enhance cancer immunotherapy efficacy: molecular mechanisms and clinical advances.Medical oncology (Northwood, London, England) · 2025Pooled it
- TAPISTRY: A Phase II Study of Atezolizumab in Patients with Tumor Mutational Burden-High Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- A Randomized Phase II Study: CRS207/GVAX plus Anti-PD-1 and Anti-CTLA4 Recruits Mesothelin- and mKRAS-Specific T Cells into PDAC.Cancer immunology research · 2026Trial
- Gemogenovatucel-T Advantage in Clonal Tumor Mutation Burden-High Ovarian Cancer.JCO precision oncology · 2026Trial
- Phase 2 Trial of PD-1 Inhibitor Sintilimab in Recurrent/Progressive Meningioma.CNS neuroscience & therapeutics · 2025Trial
- Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: a randomized phase 2 trial.Nature medicine · 2025Trial
- DNA prime and peptide boost immunization elicits robust neoantigen-specific CD8Oncoimmunology · 2026Article
- A relative methylation ordering biomarker of lactylation-related genes predicts prognosis and therapeutic response in cutaneous melanoma.Epigenetics · 2026Article
- xinguangA preliminary characterization of PI4K/PIPK alterations across solid tumors: an exploratory framework for prognostic and therapeutic stratification.Cancer biology & therapy · 2026Article
- Artificial intelligence in immune checkpoint inhibitor research: A bibliometric analysis of the landscape.Human vaccines & immunotherapeutics · 2026Article
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Role of tumor necrosis factor receptor superfamily member 19 in cancer: Diverse functions and therapeutic potential (Review).Oncology letters · 2026Review
- Nivolumab in patients with advanced solid tumors with ctDNA-defined high blood tumor mutational burden: a phase II trial.ESMO open · 2026Article
- Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.Acta oncologica (Stockholm, Sweden) · 2026Article
- Prevalence of High Programmed Death-Ligand 1 Expression in Pulmonary Sarcomatoid Carcinoma: A Systematic Review and Meta-Analysis.JTO clinical and research reports · 2026Review
- Tumor-Type-Specific Tumor Mutational Burden Cutoffs for Improved Immune Checkpoint Inhibitor Outcome Prediction: Large-Scale Analysis with Real-World Targeted Next-Generation Sequencing Data.Cancer research and treatment · 2026Article
4,817 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Naiyer A RizviDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. chant@mskcc.org.
Matthew D HellmannDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA.
Alexandra SnyderDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pia KvistborgDivision of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Vladimir MakarovHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jonathan J HavelHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
William LeeDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jianda YuanImmune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Phillip WongImmune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Teresa S HoImmune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Martin L MillerComputation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Natasha RekhtmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Andre L MoreiraDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Fawzia IbrahimDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cameron BruggemanDepartment of Mathematics, Columbia University, New York, NY, 10027, USA.
Billel GasmiLudwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Roberta ZappasodiLudwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yuka MaedaLudwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Chris SanderComputation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Edward B GaronDavid Geffen School of Medicine at UCLA, 2825 Santa Monica Boulevard, Suite 200, Santa Monica, CA 90404, USA.
Taha MerghoubDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jedd D WolchokDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ton N SchumacherDivision of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Timothy A ChanWeill Cornell Medical College, New York, NY, 10065, USA. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. chant@mskcc.org.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTranslational Research in Oncology Training ProgramT32CA160001 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SAWYERS, CHARLES L. · 2011 to 2020
$2.0MInhibiting EGFR and ER pathways in NSCLCK23CA149079 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GARON, EDWARD B · 2011 to 2015
$826kCancer Research UK 21141NCI NIH HHS K23 CA149079NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA160001
Abstract
Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti-PD-1 therapy.
Indexed as
Antibodies, Monoclonal, HumanizedAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesCohort StudiesDisease-Free SurvivalDNA RepairDrug Resistance, NeoplasmHumansLung NeoplasmsMutationProgrammed Cell Death 1 ReceptorSmokingAntibodies, Monoclonal, HumanizedAntineoplastic AgentsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor
Identifiers
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Registered trials
NCT02710396ClinicalTrials.gov
NCT02869802ClinicalTrials.gov
NCT02963090ClinicalTrials.gov
NCT03111732ClinicalTrials.gov
NCT03557359ClinicalTrials.gov
NCT03651271ClinicalTrials.gov
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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.