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. 2022 Feb;130(2):82-94.
doi: 10.1111/apm.13195. Epub 2021 Dec 23.

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

Mayur Parkhi  1 , Debajyoti Chatterjee  1 , Amanjit Bal  1 , Poorva Vias  2 , Budhi Singh Yadav  2 , Gaurav Prakash  3 , Sunil Kumar Gupta  4 , Bishan Dass Radotra  1
Affiliations

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

Mayur Parkhi et al. APMIS. 2022 Feb.

Abstract

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 tumor-infiltrating 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 ± 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.

Keywords: Central nervous system; PD-L1; diffuse large B-cell lymphoma; tumor microenvironment; tumor-infiltrating lymphocytes.

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References

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