PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

Re, Marzia Del; Marconcini, Riccardo; Pasquini, Giulia; Rofi, Eleonora; Vivaldi, Caterina; Bloise, Francesco; Restante, Giuliana; Arrigoni, E.; Caparello, Chiara; Bianco, Maria Grazia; Crucitta, Stefania; Petrini, Iacopo; Vasile, Enrico; Falcone, Alfredo; Danesi, Romano

doi:10.1038/bjc.2018.9

Cited by 205 publications

(175 citation statements)

References 14 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…For example, 12.Nabet et al [14] reported that an unshielded exosome (RNA RN7SL1) acts as a damage-associated molecular pattern (DAMP) to activate the pattern recognition receptor, RIG-I, to drive anti-viral signaling when transferred to recipient breast cancer cells via an exosome that ultimately leads to tumor growth and therapy resistance. The CD274 mRNA in plasmaderived EVs is related to the response to anti-PD-1 antibodies in melanoma and non-small cell lung cancer [15]. These results reveal the potential of exLRs to be applied in the diagnosis of human cancers and cell-to-cell mediators of metastasis.…”

Section: Introductionmentioning

confidence: 78%

“…It has been shown that EV long RNAs (exLRs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and messenger RNA(mRNA), are in human plasma EVs and play a vital role in the progression of tumor development [12][13][14][15]. For example, 12.Nabet et al [14] reported that an unshielded exosome (RNA RN7SL1) acts as a damage-associated molecular pattern (DAMP) to activate the pattern recognition receptor, RIG-I, to drive anti-viral signaling when transferred to recipient breast cancer cells via an exosome that ultimately leads to tumor growth and therapy resistance.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

Hua

Shen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Surgery remains the most important treatment strategy for solid tumors, such as colorectal cancer (CRC); However, a number of studies have suggested that surgical stress contributes to tumor recurrence or distant metastases. Extracellular vesicles (EVs), which contain a rich variety of RNAs with specialized functions and clinical applications, have been shown to be an indicator for diagnosis and prognosis of cancers. The effect of surgical stress on the landscape and characteristics of EV long RNA (exLR) in human blood, however, remains largely unknown.Methods: We present an optimized strategy for exLR sequencing (exLR-seq) the plasma from three patients with CRC at 4 time points (before surgery [T0], after extubation [T1], 1 day after surgery [T2], and 3 days after surgery [T4]). The “Limma” R package was used to evaluate the dynamic changes of mRNAs and long non-coding (lnc)RNAs from EVs. We also constructed a protein–protein interaction (PPI) network of hub genes and predicted biological processes, cellular components, and molecular functions of gene ontology (GO) functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results: We observed a sufficient number of exLRs, including 12,924 mRNAs and 2196 lncRNAs. Both mRNAs and lncRNAs underwent dynamic changes during the peri-operative period. Compared with T0, there were 110 mRNAs differentially expressed after extubation, 60 differentially expressed genes（DEGs）1 day after surgery, and 50 DEGs 3 days after surgery. A total of 11 genes changed at all 3 time points and were related to regulation of the membrane potential, receptor complex, and passive transmembrane transporter activity. In addition, 22 lncRNAs were differentially expressed after extubation (T1). Nineteen lncRNAs were differentially expressed between T0 and T2, and 38 lncRNAs were differentially expressed between T0 and T3. In addition, we found that only 3 lncRNAs changed at 3 time points. Interestingly, blood exLRs reflected the tissue origins and relative fractions of different immune cell types. EVs from CD8+ T，CD4+ memory T, and NK cells decreased after surgery and the absolute quality of EVs from immune cells decreased as well. Conclusion: In summary, this study demonstrated abundant exLRs in human plasma and the dynamic changes of these exLRs and exLRs originating from CD8+ T and CD4+ memory T cells were reduced during the peri-operative period.

show abstract

Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

Hua

Shen

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The FDA has approved PD-L1 immunohistochemistry as a companion diagnostic indicator for anti-PD-1 therapy in patients with non-small cell lung cancer (NSCLC) (24)(25)(26). Programmed death 1 ligand on the tumorderived exosomes released from some types of tumor is involved in the immune evasion of tumor cells (27)(28)(29). In the preclinical model of colorectal cancer, administration of PD-L1 antibody in combination with the inhibition of exosomal PD-L1 secretion could achieve tumor-suppressive effects (28).…”

Section: Pd-1 Ligand Expressionmentioning

confidence: 99%

Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade

Jiang

Zhao

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Immune checkpoint inhibitors target the inhibitory receptors on T cells to reinstate their antitumor ability and have shown significant efficacy in treating various cancers. However, because of tumor heterogeneity and many other uncover reasons, the objective response rate for programmed death 1 and programmed death-ligand 1 (PD-1/PD-L1) blockade is only 20 to 30%; its response rate in solid tumors is relatively low, and different degrees of side effects have occurred. There are still many unknown factors affecting the therapeutic effectiveness of PD-1/PD-L1 blockade. Additionally, screening the responding tumor patients accurately and improving the response rate and efficacy are huge challenges for tumor precise treatment. Here, we attempt to summarize the recent progress in response prediction and combined application of PD-1/PD-L1 blockade and briefly discuss the methods and evaluations combined with PD-1/PD-L1 blockade to improve the implementation of precision immunotherapy.

show abstract

“…Melanoma patients responding to pembrolizumab could be distinguished from non-responders by increased levels of EV PD-L1 at 3 to 6 weeks after the start of therapy [97]. In another study, it was shown that exosomal PD-L1 mRNA levels decreased during nivolumab or pembrolizumab treatment of melanoma patients with complete or partial response, while in patients with progressive disease EV PD-L1 expression was increased [98].…”

Section: Predicting the Response To The Ici Therapymentioning

confidence: 99%

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

View full text Add to dashboard Cite

Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

show abstract

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

Abstract: This corrects the article DOI: 10.1038/bjc.2017.85.

Cited by 205 publications

References 14 publications

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

Progress and Challenges in Precise Treatment of Tumors With PD-1/PD-L1 Blockade

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Contact Info

Product

Resources

About