Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders

Abstract

The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56bright NK-cells that serve a regulatory function and more mature, circulating CD56dim NK-cells with effector cytolytic properties. CD56bright NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCRαβ+ and CD8αβ+ TCRαβ+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type ‘a’ IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8αα and innate lymphoid cells that lack TCRs. The central feature of type ‘b’ IELs is the expression of CD8αα homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8αα+ TCRαβ+ and CD8αα+ TCRγδ+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report

“…Intestinal NKTCL, as a category of extranodal lymphoma, has a low incidence, accounting for approximately 8%-15% of GI lymphomas, but has a poor prognosis[ 2 , 4 ]. Intestinal NKTCL is mostly associated with EBV infection, and its incidence is characterized by distinct ethnic groups and regional distributions; it is more prevalent in the East and in South America, but with a low overall incidence[ 5 ].…”

“…Intestinal natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive lymphoma[ 1 ]. NKTCL accounts for approximately 8%-15% of all gastrointestinal (GI) lymphomas[ 2 ]. Today, Asian populations are more likely to develop Epstein-Barr virus (EBV)-associated subtypes of non-Hodgkin's lymphoma, a situation that appears to be related to geographic location[ 3 ].…”