"Don't Eat me" Signal in Hematological Malignancies: CD24 as New Target to Improve Anti-cancer Immunity.

Mantle-cell Lymphoma (MCL) is a B-cell non-Hodgkin's lymphoma (NHL) with heterogeneous behavior,ranging from indolent phenotype to highly aggressive and drug resistant cases with dismal prognosis.Disease progression and drug resistance may be generated by Tumor Microenvironment (TME),owing that M2-like immunosuppressive tumor associated macrophages (TAM) are pathologically functional in providing survival signals to MCL cells-and TME is known to help mask tumoral cells from host immune system.Similarly, Chronic Lymphocytic Leukemia (CLL) is a B-cell malignancy characterized by increased circulating number of mature B lymphocytes that eventually reside into bone marrow and lymphoid tissues as well.Higher number of circulating abnormal B cells is secondary to a balance between increased proliferation and decreased apoptosis activities,sustained by signals also deriving from TME.As a matter of fact,TME harbors different cell compounds and monocyte-derived Nurse-like cells (NLCs) resemble the M2-like macrophage immunosuppressive profile and turned out to be an important component able to interact with CLL cells, providing improvement of proliferation and survival.Recently, cancer-expressed CD47 was found to be involved in tumor immune escape through interaction with Signal Regulatory Protein-α (SIRP-α) expressed by TAM,being able to quench phagocytosis. Interestingly,"Don't Eat Me" signal (DEMs) blockade with anti-CD47 monoclonal Antibody (mAb) showed promising activity in pretreated NHL,through increase of phagocytosis by TAM.CD24 was also demonstrated to be involved in DEMs in solid cancer.As a matter of fact, tumor-expressed CD24 promotes immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin10 (Siglec-10),expressed by TAM with immunosuppressive phenotype (M2-like).In a preclinical model of CD24+ solid tumors (ovarian and breast cancer) the blockade of CD24-Siglec-10 interaction with anti-CD24 mAb showed improvement of TAM-associated phagocytosis in vitro and TAM-dependent reduction of tumor growth and increase of survival in vivo.It is worth mentioning that CD24 can be expressed in some phases of B-cell differentiation and both MCL and CLL derives from a B-cell precursor with upregulated CD24.In this setting,CD24 might play a critical role in the anti-phagocytic signal, since MCL and CLL represents a subset of B-cell malignancies with a considerable hostile TME with M2-like TAM,able to jeopardize anti-cancer immunity.Therefore, the possibility to boost innate anti-cancer immunity through this DEMs blockade could provide new therapeutic options to previous heavily pretreated relapsed/refractory MCL and CLL patients.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

Patient inclusion criteria:

* Signed and dated EC-approved informed consent
* Diagnosis of Mantle-cell Lymphoma (MCL) or B-cell Chronic Lymphocytic Leukemia (CLL) defined according to World Health Organization (WHO) criteria.
* Female or male, 18 years of age or older.
* ECOG performance status 0-3.
* Willingness and ability to comply with routine clinical practice and study procedures.

Donors inclusion criteria:

* Signed and dated EC-approved informed consent.
* Healthy volunteers agreed to undergo plateletpheresis.
* Female or male, 18 years of age or older.
* Willingness and ability to comply with Transfusion Medicine clinical practice and study procedures.

Exclusion Criteria

Patient exclusion criteria:

* Other hematological diseases defined by WHO criteria different from MCL and CLL.
* Previous treatment regimens that included allogeneic stem cell transplantation (ASCT).

Donors exclusion criteria:

-Healthy volunteers agreed to perform any kind of donations with the exception of plateletpheresis.