Co-Expression of MYC, BCL2 and PD-L1 in Primary Central Nervous System Diffuse Large B Cell Lymphomas ( PCNSL)

Background

Increased protein expression and gene translocations of MYC and BCL2/BCL6promote increased cell growth and inhibit apoptosis. They are associated with inferior prognosis in systemic diffuse large B cell lymphomas (DLBCLs). Their role in primary PCNSLs however is less clear. The immune checkpoint molecules, programmed death 1 (PD1) and its ligand PD-L1 are involved in inhibitory pathways to maintain immune tolerance and it is now clear that tumor cells interfere with these pathways to promote escape from immune surveillance. Antibody blockade of these immune checkpoints has been shown to enhance antitumor immunity and is emerging as an important target for cancer immunotherapy. We examined the co expression of these proteins on tumor samples from patients with PCNSL .

Methods

Immunohistochemistry (IHC) for MYC, BCL2 and PDL-1 and florescence in situ hybridization ( FISH) for MYC (8q24), BCL2 ( 18q21) and BCL6 (3q27) were performed on tumor samples from 14 patients with PCNSL.

Results

Eleven patients were positive for PDL-1 (79%) by IHC. Of these eleven patients, six (55%) were also positive for both MYC and BCL2 by IHC and negative by FISH. Eight patients (57%) were positive for MYC and BCL2 by IHC but negative for PD-L1. One patient was positive by FISH for MYC, BCL2, and BCL6 but negative for PDL-1.

Conclusions

Our results, although in a small number of patients, demonstrate that a large percentage of patients with PCNSL who express MYC and BCL2 also express PD-L1.It has been suggested that the frequent over expression of MYC, BCL2, and BCL6 noted in PCNSL may underlie the inferior prognosis as compared to systemic DLBCL. We suggest that the co-expression of MYC/ BCL2 with PD-L1 may contribute to this poor prognosis by engaging the complimentary mechanisms of increasing cell growth, inhibiting apoptosis and evading immune surveillance. The use of PD-L1 inhibitors in hematologic malignancies is limited but has demonstrated clinical responses in relapsed/refractory disease following multiple lines of therapy and warrants further investigation in PCNSLs.

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