PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients
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 liter...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.613007/full |
| _version_ | 1818420064991313920 |
|---|---|
| author | Federica Costa Rosanna Vescovini Valentina Marchica Paola Storti Laura Notarfranchi Laura Notarfranchi Benedetta Dalla Palma Benedetta Dalla Palma Denise Toscani Jessica Burroughs-Garcia Maria Teresa Catarozzo Gabriella Sammarelli Nicola Giuliani Nicola Giuliani |
| author_facet | Federica Costa Rosanna Vescovini Valentina Marchica Paola Storti Laura Notarfranchi Laura Notarfranchi Benedetta Dalla Palma Benedetta Dalla Palma Denise Toscani Jessica Burroughs-Garcia Maria Teresa Catarozzo Gabriella Sammarelli Nicola Giuliani Nicola Giuliani |
| author_sort | Federica Costa |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T12:48:32Z |
| format | Article |
| id | doaj.art-3c1062e0feab4993a5f3121920a18f56 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:48:32Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3c1062e0feab4993a5f3121920a18f562022-12-21T23:00:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.613007613007PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma PatientsFederica Costa0Rosanna Vescovini1Valentina Marchica2Paola Storti3Laura Notarfranchi4Laura Notarfranchi5Benedetta Dalla Palma6Benedetta Dalla Palma7Denise Toscani8Jessica Burroughs-Garcia9Maria Teresa Catarozzo10Gabriella Sammarelli11Nicola Giuliani12Nicola Giuliani13Department of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, ItalyBackgroundThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.613007/fullmultiple myelomaprogrammed cell death protein-1programmed cell death protein-ligand 1smoldering myelomaimmune checkpoint |
| spellingShingle | Federica Costa Rosanna Vescovini Valentina Marchica Paola Storti Laura Notarfranchi Laura Notarfranchi Benedetta Dalla Palma Benedetta Dalla Palma Denise Toscani Jessica Burroughs-Garcia Maria Teresa Catarozzo Gabriella Sammarelli Nicola Giuliani Nicola Giuliani PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients Frontiers in Immunology multiple myeloma programmed cell death protein-1 programmed cell death protein-ligand 1 smoldering myeloma immune checkpoint |
| title | PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients |
| title_full | PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients |
| title_fullStr | PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients |
| title_full_unstemmed | PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients |
| title_short | PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients |
| title_sort | pd l1 pd 1 pattern of expression within the bone marrow immune microenvironment in smoldering myeloma and active multiple myeloma patients |
| topic | multiple myeloma programmed cell death protein-1 programmed cell death protein-ligand 1 smoldering myeloma immune checkpoint |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.613007/full |
| work_keys_str_mv | AT federicacosta pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT rosannavescovini pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT valentinamarchica pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT paolastorti pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT lauranotarfranchi pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT lauranotarfranchi pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT benedettadallapalma pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT benedettadallapalma pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT denisetoscani pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT jessicaburroughsgarcia pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT mariateresacatarozzo pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT gabriellasammarelli pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT nicolagiuliani pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients AT nicolagiuliani pdl1pd1patternofexpressionwithinthebonemarrowimmunemicroenvironmentinsmolderingmyelomaandactivemultiplemyelomapatients |