Background

Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and PD-L1 expression in the PCNSL and evaluated their prognostic significance.

Materials and Methods

All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1 and PD-L1 was performed on tissue microarray.

Result

Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male-to-female ratio of 0.91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells was significantly associated with the longer OS (p=0.037) and DFS (p=0.023). TAMs (68CD and CD163 positive) showed inverse relationship with OS and DFS but didn’t reach statistical significance (p>0.05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p=0.037).

Conclusion

TME plays significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1 expressing immune cells are associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against TME and immune check point inhibitors in this disease.