ArticleCancer discovery2016
Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy.
2 registry-linked trialsOpen access · greenAbstract read
In one paragraph
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,006 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
1,006citing papers in PubMed, 1 pooled it
41.4field-weighted citation impact, top 1% of its field
What it found
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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.
Canadian Atezolizumab Precision Targeting for Immunotherapy Intervention
The Study of Microglia/Macrophages Involved Dynamic Evolution of Glioma Microenvironment and the Function and Visualization of Targeted Molecules of Glioma
Who cites it
1,006 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,506 citations in OpenAlex.
- Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma - a multicenter phase 2 trial (EPOC1802).Nature cancer · 2025Trial
- Overcoming melanoma drug resistance: Mechanisms and clinical progress of oncolytic viruses combined with immune checkpoint inhibitors (Review).Oncology reports · 2026Review
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- ClonalLife science alliance · 2026Article
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework.Redox biology · 2026Review
- New and emerging strategies for targeting cancers: Challenges and opportunities (Review).Oncology letters · 2026Review
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- Genetic Ablation and Multi-Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HLA Class I Expression Is Associated with Increased Immune Cell Density and PTEN Loss in Prostate Cancer.Molecular cancer research : MCR · 2026Article
- Phase I Trial of Ipatasertib plus Atezolizumab Enhances PI3K/AKT Pathway Immune Responses in Solid Tumors and Refractory Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
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- Multi-omics profiling unveils biological and clinical insights into pulmonary sarcomatoid carcinoma.Cell reports. Medicine · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
946 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
44 authors at 3 institutions in 1 country.
Weiyi PengDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jie Qing ChenDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Chengwen LiuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Shruti MaluDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Caitlin CreasyDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Michael T TetzlaffDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Chunyu XuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jodi A McKenzieDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Chunlei ZhangDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Xiaoxuan LiangDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Leila J WilliamsDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Wanleng DengDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Guo ChenDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rina MbofungDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Alexander J LazarDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Carlos A Torres-CabalaDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Zachary A CooperDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Pei-Ling ChenDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Trang N TieuInstitute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Stefani SprangerDepartment of Pathology, University of Chicago, Chicago, Illinois.
Xiaoxing YuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Chantale BernatchezDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Marie-Andree ForgetDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cara HaymakerDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rodabe AmariaDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jennifer L McQuadeDivision of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Isabella C GlitzaDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Tina CasconeDivision of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Haiyan S LiDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Lawrence N KwongDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Timothy P HeffernanInstitute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jianhua HuDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Roland L BassettDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Marcus W BosenbergDepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Scott E WoodmanDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Willem W OverwijkDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Gregory LizéeDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jason RoszikDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Thomas F GajewskiDepartment of Pathology, University of Chicago, Chicago, Illinois.
Jennifer A WargoDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jeffrey E GershenwaldDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Laszlo RadvanyiDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Michael A DaviesDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. phwu@mdanderson.org mdavies@mdanderson.org.
Patrick HwuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. phwu@mdanderson.org mdavies@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USUniversity of Illinois Chicago · USYale University · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MYale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0MUT M.D. Anderson Cancer Center SPORE in MelanomaP50CA093459 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GRIMM, ELIZABETH A · 2004 to 2014
$23.7MCenter for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4MTRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8MMolecular Mechanisms of pDC InteractionsP01CA128913 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BEKELE, BENJAMIN NEBIYOU · 2008 to 2012
$9.3MRole of Tumor Stroma in Therapeutic Response and ResistanceU54CA163125 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FLAHERTY, KEITH T, FUTREAL, PHILLIP ANDREW · 2011 to 2015
$4.4MTransduction of T-cells to improve migration to tumorR01CA116206 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HWU, PATRICK · 2005 to 2014
$3.2MThe role of the PI3K pathway in immune resistanceR01CA187076 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL, HWU, PATRICK · 2014 to 2018
$2.0MThe Role of the PI3K-AKT Pathway in Melanoma Brain MetastasisR01CA154710 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL · 2011 to 2015
$1.6MTumor-intrinsic oncogenic alterations and evasion of anti-tumor immunityR00CA204595 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SPRANGER, STEFANI · 2017 to 2019
$747kExploring synergy of combined BRAF-targeted therapy & immunotherapy for melanomaK08CA160692 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WARGO, JENNIFER A. · 2012 to 2016
$713kNCATS NIH HHS UL1 TR000371NCI NIH HHS 1K08CA160692-01A1NCI NIH HHS K08 CA160692NCI NIH HHS K99 CA204595NCI NIH HHS P01 CA128913NCI NIH HHS P01CA128913NCI NIH HHS P30 CA016359NCI NIH HHS P30 CA016672NCI NIH HHS P30CA016672NCI NIH HHS P50 CA093459NCI NIH HHS P50CA093459NCI NIH HHS R00 CA204595NCI NIH HHS R01 CA116206NCI NIH HHS R01CA116206NCI NIH HHS R01 CA154710NCI NIH HHS R01CA154710NCI NIH HHS R01 CA187076NCI NIH HHS R01CA187076NCI NIH HHS T32 CA009666NCI NIH HHS U54 CA163125NCI NIH HHS U54CA163125-01
Abstract
unlabelledT cell-mediated immunotherapies are promising cancer treatments. However, most patients still fail to respond to these therapies. The molecular determinants of immune resistance are poorly understood. We show that loss of PTEN in tumor cells in preclinical models of melanoma inhibits T cell-mediated tumor killing and decreases T-cell trafficking into tumors. In patients, PTEN loss correlates with decreased T-cell infiltration at tumor sites, reduced likelihood of successful T-cell expansion from resected tumors, and inferior outcomes with PD-1 inhibitor therapy. PTEN loss in tumor cells increased the expression of immunosuppressive cytokines, resulting in decreased T-cell infiltration in tumors, and inhibited autophagy, which decreased T cell-mediated cell death. Treatment with a selective PI3Kβ inhibitor improved the efficacy of both anti-PD-1 and anti-CTLA-4 antibodies in murine models. Together, these findings demonstrate that PTEN loss promotes immune resistance and support the rationale to explore combinations of immunotherapies and PI3K-AKT pathway inhibitors. SIGNIFICANCE: This study adds to the growing evidence that oncogenic pathways in tumors can promote resistance to the antitumor immune response. As PTEN loss and PI3K-AKT pathway activation occur in multiple tumor types, the results support the rationale to further evaluate combinatorial strategies targeting the PI3K-AKT pathway to increase the efficacy of immunotherapy.
Indexed as
AminopyridinesAnimalsAntibodiesCell Line, TumorCTLA-4 AntigenDrug Resistance, NeoplasmDrug SynergismHumansImmunotherapyMelanomaMiceMorpholinesProgrammed Cell Death 1 ReceptorPTEN PhosphohydrolaseT-LymphocytesAminopyridinesAntibodiesCTLA-4 AntigenCtla4 protein, mouseMorpholinesNVP-BKM120Pdcd1 protein, mouseProgrammed Cell Death 1 ReceptorPTEN PhosphohydrolasePTEN protein, human
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Registered trials
NCT04273061ClinicalTrials.gov
NCT04781764ClinicalTrials.gov
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.