PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma

Crescenzi, Anna; Annibali, Ombretta; Bianchi, Antonella; Pagano, Anastasia; Donati, Michele; Grifoni, Alba; Avvisati, Giuseppe

doi:10.1016/j.leukres.2016.09.008

Cited by 7 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, bone marrow (BM) stromal cells induce myeloma cells to express PD-L1, inducing increased tumor cell proliferation and reduced susceptibility to chemotherapy (17). PD-L1 expression is often detected on plasma cells in extramedullary plasmacytomas of late-stage disease (18). Furthermore, PD-1 levels on T cells in myeloma patients are negatively correlated with survival (19), and PD-L1 upregulation on MM cells is common among patients with relapsed or refractory MM and associated with an aggressive phenotype (20).…”

Section: Introductionmentioning

confidence: 99%

Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial

et al. 2020

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial

et al. 2020

View full text Add to dashboard Cite

“…This finding also suggested that the activation of the PD-L1 pathway correlates with disease relapse. Crescenzi et al evaluated the expression of PD-L1 with immunohistochemistry staining in extra-medullary multiple myeloma lesions and suggested a possible link to poor prognosis [13]. However, the measurement of soluble PD-L1 is not available in the vast majority of clinical laboratories.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of the Dynamic Change of Programmed Death-ligand 1 Expression in Patients with Multiple Myeloma

Guan

Wang

Hasan

et al. 2019

Cureus

View full text Add to dashboard Cite

Background The inhibition of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway has been shown to be an effective targeted therapy in fighting both solid organ cancers and hematological malignancies. PD-L1 expression also serves as a prognostic marker in various cancers. However, the expression of PD-L1 and its prognostic significance in multiple myeloma remains largely unknown. Methods Immunohistochemistry staining of PD-L1 was performed in bone marrow biopsy samples (total of 85 samples) in 32 myeloma patients receiving autologous stem cell transplant (ASCT) at various time points: before ASCT, post-ASCT, and/or at relapse after ASCT. More than 1% of myeloma cells with PD-L1 staining was considered a positive expression of PD-L1. A correlation analysis was performed between post-ASCT overall survival (OS) and the status of PD-L1 expression. Results In this pilot study, a total of 11 patients (34%) out of our cohort (32 patients) were positive for PD-L1 expression at least once during the course of the disease. A dynamic change of PD-L1 expression was noted in three patients converting from negative (before ASCT) to positive (post-ASCT) and two patients converting from positive (before ASCT) to negative (post-ASCT). Patients with positive PD-L1 expression persisting or occurring post-ASCT had shorter post-ASCT overall survival than those with negative PD-L1 expression post-ASCT (median survival: 13 vs 23 months, p<0.05). No significant differences were detected in the known prognostic factors between these two groups at the time of ASCT. Pre-transplant PD-L1 expression status, however, showed no significant impact on post-ASCT overall survival. Furthermore, a few patients switching from positive PD-L1 expression before ASCT to negative PD-L1 expression post-ASCT had a relatively good post-ASCT overall survival (n=2, overall survival of 29 and 56 months, respectively). Conclusion Immunohistochemistry can be reliably used for measuring PD-L1 expression in decalcified marrow core biopsy materials. Our results suggest that positive PD-L1 expression persisting/occurring post-ASCT could be an adverse prognostic marker for post-ASCT OS. Additionally, PD-L1 expression appears to be dynamic and is subjected to change after ASCT. Our findings suggest that periodically monitoring PD-L1 expression in patients with multiple myeloma post-ASCT is warranted. Further studies are needed to confirm our initial observation and to evaluate if timely intervention with PD-L1 blockade can improve post-ASCT outcomes in myeloma patients.

show abstract

“…PD-L1 expression was also detected by immunohistochemistry on PCs from patients with extra-medullary disease, together with PD-1+ T cells infiltrating the extra-medullary lesions, suggesting a possible link between the PD-L1/PD-1 axis and a poor prognosis [47]. However, further studies are needed to clarify the involvement of this checkpoint in the onset of extra-medullary disease.…”

Section: Pd-l1/pd-1 Distribution In MM Microenvironmentmentioning

confidence: 99%

PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Costa

Marchica

Storti

et al. 2021

Cancers

View full text Add to dashboard Cite

The emerging role of the PD-1/PD-L1 axis in MM immune-microenvironment has been highlighted by several studies. However, discordant data have been reported on PD-1/PD-L1 distribution within the bone marrow (BM) microenvironment of patients with monoclonal gammopathies. In addition, the efficacy of PD-1/PD-L1 blockade as a therapeutic strategy to reverse myeloma immune suppression and inhibit myeloma cell survival still remains unknown. Recent data suggest that, among the potential mechanisms behind the lack of responsiveness or resistance to anti-PD-L1/PD-1 antibodies, the CD38 metabolic pathways involving the immune-suppressive factor, adenosine, could play an important role. This review summarizes the available data on PD-1/PD-L1 expression in patients with MM, reporting the main mechanisms of regulation of PD-1/PD-L1 axis. The possible link between the CD38 and PD-1/PD-L1 pathways is also reported, highlighting the rationale for the potential use of a combined therapeutic approach with CD38 blocking agents and anti-PD-1/PD-L1 antibodies in order to improve their anti-tumoral effect in MM patients.

show abstract

PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma

Cited by 7 publications

References 14 publications

Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial

Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial

Prognostic Significance of the Dynamic Change of Programmed Death-ligand 1 Expression in Patients with Multiple Myeloma

PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Contact Info

Product

Resources

About