ArticleCancer immunology, immunotherapy : CII2017
The PD-L1/PD-1 pathway promotes dysfunction, but not "exhaustion", in tumor-responding T cells from pleural effusions in lung cancer patients.
Article in Cancer immunology, immunotherapy : CII, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Pleural effusion volume as a novel biomarker for prognostic and therapeutic stratification in small cell lung cancer: a translationally-focused cohort study.Translational lung cancer research · 2026Article
- Unraveling the multidimensional pleural ecosystem of lung cancer-associated malignant pleural effusion.Cancer cell international · 2026Review
- Efficacy of FOXP3+Treg cells combined with platelet in predicting recurrence of cervical cancer: a retrospective study.BMC women's health · 2026Article
- Emerging immunotherapeutic strategies for malignant serous effusions: current evidence and future directions.Frontiers in oncology · 2026Review
- Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients.Oxford open immunology · 2026Article
- Circulating stem-like exhausted CD8 T cells point to better outcomes in lung cancer: a brief report.Translational lung cancer research · 2025Article
- A review of enhanced biosignature immunotherapy tools for predicting lung cancer immune phenotypes using deep learning.Discover oncology · 2025Review
- Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.Translational lung cancer research · 2024Article
- Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions.Clinical and experimental medicine · 2024Article
- Immunotherapy of Clear-Cell Renal-Cell Carcinoma.Cancers · 2024Review
- Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications.Cancer cell international · 2024Review
- Candidate tumor-specific CD8Oncoimmunology · 2024Article
- The role of CD4MedComm · 2023Review
- A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis.Signal transduction and targeted therapy · 2022Article
- The Detection of Immunity against WT1 and SMAD4International journal of molecular sciences · 2022Article
- Clinical Value of the PD-1/PD-L1/PD-L2 Pathway in Patients Suffering from Endometriosis.International journal of molecular sciences · 2022Article
- CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- Malignant Pleural Effusions-A Window Into Local Anti-Tumor T Cell Immunity?Frontiers in oncology · 2021Review
- Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR-mutated non-small cell lung cancer patient: A case report.Thoracic cancer · 2020Article
- Characteristics of Malignant Pleural Effusion Resident CD8International journal of molecular sciences · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts. PD-L1 was up-regulated in lung cancer cell lines upon treatment with IFN-gamma, but not under hypoxic conditions, as detected by RT-qPCR and flow cytometry. Blockade of PD-L1 on tumor cells restored granzyme-B expression in allogenic CD8+ T cells in vitro. Remarkably, pleural effusion CD8+ T cells that responded to the tumor antigens MAGE-3A and WT-1 (identified as CD137+ cells) were lower in frequency than CMV pp65-responding CD8+ T cells and did not have an exhausted phenotype (PD-1+ TIM-3+). Nonetheless, tumor-responding CD8+ T cells had a memory phenotype and expressed higher levels of PD-1. A PD-L1 blocking antibody increased the expression of granzyme-B and perforin on polyclonal- and tumor-stimulated CD8+ T cells. Taken together, our data show that rather than being exhausted, tumor-responding CD8+ T cells are not completely differentiated into effector cells and are prone to negative regulation by PD-L1. Hence, our study provides evidence that lung cancer patients respond to immunotherapy due to blockade of the PD-L1/PD-1 pathway.
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