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PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

ABSTRACT: PD-L1 expression is associated with poor prognosis, although this relationship is unclear in bone marrow-derived haematologic malignancies, including multiple myeloma. We aimed to determine whether PD-L1 expression could predict the prognosis of newly diagnosed multiple myeloma (NDMM). We evaluated 126 NDMM patients (83, retrospectively; 43, prospectively) who underwent bone marrow examinations. Bone marrow aspirates were analysed for PD-L1 expression, categorized as low or high expression, using quantitative immunofluorescence. High PD-L1 expression could independently predict poor overall survival (OS) (95% CI?=?1.692-8.346) in multivariate analysis. On subgroup analysis, high PD-L1 expression was associated with poor OS (95% CI?=?2.283-8.761) and progression-free survival (95% CI?=?1.024-3.484) in patients who did not undergo autologous stem cell transplantation (ASCT) compared with those who did. High PD-L1 expression was associated with poor OS despite frontline treatments with or without immunomodulators. Thus, PD-L1 expression can be a useful prognosis predictor in NDMM patients, whereas ASCT may be used in patients with high PD-L1 expression. We developed a prognostic nomogram and found that a combination of PD-L1 expression in bone marrow plasma cells and clinical parameters (age, cytogenetics, and lactate dehydrogenase) effectively predicted NDMM prognosis. We believe that our nomogram can help identify high-risk patients and select appropriate treatments.

SUBMITTER: Lee BH

PROVIDER: S-EPMC7387472 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

Lee Byung-Hyun BH Park Yong Y Kim Ji Hye JH Kang Ka-Won KW Lee Seung Jin SJ Kim Seok Jin SJ Kim Byung Soo BS

Scientific reports 20200728 1

PD-L1 expression is associated with poor prognosis, although this relationship is unclear in bone marrow-derived haematologic malignancies, including multiple myeloma. We aimed to determine whether PD-L1 expression could predict the prognosis of newly diagnosed multiple myeloma (NDMM). We evaluated 126 NDMM patients (83, retrospectively; 43, prospectively) who underwent bone marrow examinations. Bone marrow aspirates were analysed for PD-L1 expression, categorized as low or high expression, usin ...[more]

PMID: 32724129

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Project description:BackgroundThe PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies.MethodsThe PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients.ResultsFirst, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16- cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between %CD14+PD-L1+ and %CD8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells.ConclusionsOur data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment.

Project description:The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.We assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.A significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1. Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.

Dataset Information

PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

Publications

PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

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