4.6 Review

Testicular Diffuse Large B-Cell Lymphoma-Clinical, Molecular, and Immunological Features

Journal

CANCERS
Volume 13, Issue 16, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13164049

Keywords

testicular diffuse large B-cell lymphoma; lymphoma immunology; tumor micro-environment

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Funding

  1. University of Helsinki

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Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive lymphoma that mainly affects elderly men, with a high relapse rate. It presents in an immune-privileged site of the testis, with unique biology and immune-related characteristics. Studies on the tumor microenvironment and immune checkpoint inhibitors show promising results for the treatment of T-DLBCL.
Simple Summary Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive lymphoma entity that mainly affects elderly men. It has a high relapse rate with especially the relapses of the central nervous system associating with dismal outcome. T-DLBCL has a unique biology with distinct genetic characteristics and clinical presentation, and the increasing knowledge on the tumor microenvironment of T-DLBCL highlights the significance of the host immunity and immune escape in this rare lymphoma, presenting in an immune-privileged site of the testis. This review provides an update on the latest progress made in T-DLBCL research and summarizes the clinical perspectives in T-DLBCL. Primary testicular lymphoma is a rare lymphoma entity, yet it is the most common testicular malignancy among elderly men. The majority of the cases represent non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) with aggressive clinical behavior and a relatively high relapse rate. Due to the rareness of the disease, no randomized clinical trials have been conducted and the currently recognized standard of care is based on retrospective analyses and few phase II trials. During recent years, the tumor microenvironment (TME) and tumor-related immunity have been the focus of many tumor biology studies, and the emergence of targeted therapies and checkpoint inhibitors has significantly modulated the field of cancer therapies. Testicular DLBCL (T-DLBCL) is presented in an immune-privileged site of the testis, and the roles of NF-kappa B pathway signaling, 9p24.1 aberrations, and tumor-infiltrating immune cells, especially immune checkpoint expressing lymphocytes and macrophages, seem to be unique compared to other lymphoma entities. Preliminary data on the use of immune checkpoint inhibitors in the treatment of T-DLBCL are promising and more studies are ongoing.

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