Immunomodulating properties of PD-L1 positive cancer stem cells in metastatic lymph nodes

In this study we investigated correlations between the presence of PD-L1+ LCSCs and changes in T cell frequencies and immunomodulatory molecules in metastatic and non-metastatic LNs of NSCLC patients.Methods: LNs aspirates were obtained during EBUS TBNA procedure of 20 NSCLC patients. LCSC subsets and T cell characteristics were determined by flow cytometry.Results: Metastatic LNs contained a higher proportion of PD-L1+ LCSCs (1,625-6,535%), as compared to non-metastatic LNs (0-0,06%). Additionally metastatic LNs contained a lower percentage of CD4 T cells, whereas the percentage of CD8 T cells and Tregs was increased as compared to non-metastatic LNs. Also, specifically CD4 T cells in metastatic LNs expressed more PD1 and TIM3, but had a lower expression of CD28. Surprisingly, the percentage of PD-L1+ LCSCs positively correlated with the percentage of Tregs, PD-1+ CD4 T cells and Tim3+ CD4 T cells, whereas PD-L1+ LCSCs were negatively correlated with CD4 T cells and CD28+ CD4 T cells.Discussion: Our results show that PD-L1+ LCSCs strongly associates with an altered T cell distribution and phenotype in metastatic LNs of NSCLC patients, indicating that LCSCs can affect the immune system even outside the TME, which could be of importance for the response upon immunotherapy.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung cancer Source Type: research

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ConclusionsWe predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally,TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
AbstractImmunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers. One of the critical factors that influence the efficacy of immunotherapy is the tumor microenvironment (TME), which contains a hete...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Emily Roarty Jing Wang Fei Yang Michelle Barton Jeffrey Rosen Sendurai Mani Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Lei Shang1,2 and Minjie Wei1* 1School of Pharmacy, China Medical University, Shenyang, China 2Shenyang Medical College, Shenyang, China The protein lysine methyltransferase SMYD2 has recently emerged as a new enzyme modulate gene transcription or signaling pathways, and involved into tumor progression. However, the role of SMYD2 in drug resistant is still not known. Here, we found that inhibition of SMYD2 by specific inhibitor could enhance the cell sensitivity to cisplatin (CDDP), but not paclitaxel, NVB, and VCR in non-small cell lung cancer (NSCLC). Further study showed that SMYD2 and its substrates were overex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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