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TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

We examined tumours from a large cohort of patients with metastatic urothelial bladder cancer (mUC) treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical response and immune escape. Whole transcriptome profiles were generated for 368 patients using TruSeq RNA Access technology (Illumina). Somatic mutations were determined via whole exome sequencing for a subset of these patients. - Response was associated with CD8+ T effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). On the other hand, lack of response was associated with a transforming growth factor β (TGF-β) signature, particularly in patients with CD8+ T cells preferentially residing in collagen-rich matrix surrounding tumours. Integration of these three independent biological features provided the best basis for understanding outcome in this setting. -

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003977 Illumina HiSeq 2500 348
EGAD00001004218 Illumina HiSeq 2500 488
Publications Citations
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
Nature 554: 2018 544-548
LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8<sup>+</sup> T cell tumor-infiltration impairing anti-PD1 therapy.
Nat Commun 10: 2019 2416
Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.
Nat Commun 11: 2020 3800
Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer.
Breast Cancer Res Treat 188: 2021 165-178
Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.
J Immunother Cancer 9: 2021 e002231
Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers.
Sci Transl Med 13: 2021 eabe6201
<i>ACSL4</i> Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer.
Front Oncol 11: 2021 754845
Accounting for B-cell Behavior and Sampling Bias Predicts Anti-PD-L1 Response in Bladder Cancer.
Cancer Immunol Res 10: 2022 343-353
Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification.
Front Immunol 12: 2021 788959
Cell death-induced immunogenicity enhances chemoimmunotherapeutic response by converting immune-excluded into T-cell inflamed bladder tumors.
Nat Commun 13: 2022 1487
Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes.
Nat Commun 13: 2022 2127
Pyroptosis-Related Signature Predicts Prognosis and Immunotherapy Efficacy in Muscle-Invasive Bladder Cancer.
Front Immunol 13: 2022 782982
Prediction of the Immune Phenotypes of Bladder Cancer Patients for Precision Oncology.
IEEE Open J Eng Med Biol 3: 2022 47-57
Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review.
J Transl Med 20: 2022 249
Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients.
J Transl Med 20: 2022 370
Lactate: A regulator of immune microenvironment and a clinical prognosis indicator in colorectal cancer.
Front Immunol 13: 2022 876195
Conserved angio-immune subtypes of the tumor microenvironment predict response to immune checkpoint blockade therapy.
Cell Rep Med 4: 2023 100896
M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients.
Eur J Med Res 28: 2023 55
The ratio of adaptive to innate immune cells differs between genders and associates with improved prognosis and response to immunotherapy.
PLoS One 18: 2023 e0281375
Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells.
Signal Transduct Target Ther 8: 2023 164
In situ tumour arrays reveal early environmental control of cancer immunity.
Nature 618: 2023 827-833
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy.
J Immunother Cancer 11: 2023 e006941