Epic Battles in Myeloma: Deciphering the Role of PVR in the Fight Between Tumors and Cytotoxic Cells

Abstract

[eng] HYPOTHESIS: Epigenetics influence cancer and recently epigenetic plasticity has been included as a new hallmark of cancer described in the latest published work of Hanahan113. Growing scientific evidence has pointed out the importance of epigenetic regulation in immunology106 and the important role of immune checkpoint regulation in tumor recognition and clearance. As observed in clinical settings, therapeutic strategies for solid and hematological tumors often build upon each other’s successes. Solid tumors have shown greater therapeutic success in the context of immune checkpoint targeting. This is mainly due to solid tumors' well-defined TME, facilitating more effective inhibition of pathways regulating immune cell activity. Based on this, we hypothesized that an epigenetically regulated gene plays a key role in immune checkpoint regulation, which could be critical in hematological malignancies. Despite the less distinct TME in these cancers, the mechanisms of immune cell recognition remain significant. With this foundation, the following objectives were established for this thesis project.

OBJECTIVES: We have decided to divide this thesis project into three different objectives.

The overarching objective of this thesis was to study the regulation of PVR and its relation to cytotoxic activation in the context of MM. The specific objectives of this thesis are:

- Objective I: To characterize PVR’s epigenetic regulation and expression in multiple myeloma.

- Objective II: To evaluate the role of PVR in cytotoxic cell function and its impact on immunotherapy.

- Objective III: To study the effect of PVR expression alteration and its relationship with other immune checkpoint markers.