Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B‐cell lymphoma in the North Indian population

Abstract

Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population. APMIS. 2022; 130: 82-94. 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 the PD-1/ PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumorinfiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression in the PCNSL and evaluated their prognostic significance. 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 the tissue microarray. Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 AE 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, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells were significantly associated with the longer OS (p = 0.037) and DFS (p = 0.023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not 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). The TME plays a significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1-expressing immune cells is associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.

Double-hit and double-expressor primary central nervous system lymphoma: Experience from North India of an infrequent but aggressive variant

“…Majority of the cases were already worked-up for Han’s algorithm as a part of two earlier published studies. [ 8 , 9 ]…”

“…Like the previous study, the standard universal cutoffs for positivity were considered. [8,9] e IHC slides were independently evaluated by two pathologists, who were blinded to the clinical data. e cutoff for MYC, BCL6, and BCL2 positivity were taken as 40%, 50%, and 50%, respectively.…”

The prognostic value of tumor-associated macrophages detected by immunostaining in diffuse large B cell lymphoma: A meta-analysis

“…Some researchers showed that a high density of M2 TAMs was correlated with shortened survival in DLBCL (1,3,17,23). However, several other studies did not demonstrate such association (20,24,25,27,(29)(30)(31)(32). Therefore, we performed this meta-analysis to explore the role of TAMs in DLBCL progression and the prognostic value of TAMs in DLBCL patients.…”

“…Several studies showed that a high density of CD68 + TAMs was associated with favorable prognosis (3,20,21). A few other studies failed to demonstrate such association (4,18,(22)(23)(24)(25)(26)(27). By contrast, Cai et al (28) and Carreras et al (17) showed that high density of CD68 + TAMs correlated with inferior outcome.…”

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

“…There are many target receptors in PCNSL apart from B-cell antigen receptor and Toll-like receptor signaling, such as programmed cell death-1 (PD-1)/PD-1 Ligand and immune activation shown by presence of tumor infiltrating lymphocytes. So, targeting one pathway may not be sufficient to treat such a debilitating disease[ 15 , 16 ]. CSF analysis may not provide information about the tumor microenvironment.…”