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Published on: February 8, 2018
PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression
Federica Costa1, Valentina Marchica1, Paola Storti1
1Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Insights
The PD-1/PD-L1 axis impacts multiple myeloma (MM) immune suppression. Combining CD38 blocking agents with PD-1/PD-L1 therapies may enhance anti-tumor effects in MM patients.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- The PD-1/PD-L1 axis plays a role in the multiple myeloma (MM) immune microenvironment.
- Conflicting data exist regarding PD-1/PD-L1 distribution in the bone marrow of patients with monoclonal gammopathies.
- The therapeutic efficacy of PD-1/PD-L1 blockade in overcoming myeloma-induced immune suppression and inhibiting myeloma cell survival is not fully understood.
Purpose of the Study:
- To review current data on PD-1/PD-L1 expression in MM patients.
- To summarize mechanisms regulating the PD-1/PD-L1 axis.
- To explore the potential link between CD38 and PD-1/PD-L1 pathways and their therapeutic implications.
Main Methods:
- Literature review of studies on PD-1/PD-L1 expression and function in MM.
- Analysis of data on PD-1/PD-L1 distribution in the bone marrow microenvironment.
- Investigation of potential mechanisms of resistance to anti-PD-1/PD-L1 therapies, including CD38 pathways and adenosine.
Main Results:
- Discordant data on PD-1/PD-L1 expression in the MM bone marrow microenvironment.
- CD38 metabolic pathways and adenosine may contribute to resistance against anti-PD-1/PD-L1 therapies.
- A potential link exists between CD38 and PD-1/PD-L1 pathways.
Conclusions:
- The PD-1/PD-L1 axis is a significant factor in the MM immune microenvironment.
- Combined therapeutic strategies involving CD38 blocking agents and anti-PD-1/PD-L1 antibodies show promise for improving anti-tumor effects in MM patients.
Abstract:
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.
