Table 2.1.

Helicobacter-induced gastric lymphoma and bacteroides enterotoxin-induced colonic adenocarcinoma

Gastric mucosa-associated lymphoid tissue lymphoma (MALT) in Helicobacter-infected stomachs
Clinical course: Even antibiotic therapy refractory low grade MALTs seldom advance into high grade diffuse large B-cell lymphoma (DLBCL)	[730]
Complete genomic sequences of lymphomagenic H. pylori strains	[731, 732]
Chromosomal translocation t(11;18)(q21;q21) results in the formation of API12-MALT fusion oncoprotein. Oncoprotein releases cytoplasmic NFκB and activates Bcl10 nuclear gene
MALT immunophenotype: CD19+CD20+CD21+CD79a+CD5–CD10–CD23–
Micro miRNA profile: Aberrant DNA methylation of p16/INK4a gene
Methylated CpG islands:	[733, 734]
Translocations: t(1;14)(p22;q32) BCL10-IGH oncoprotein; t(14;18)(q32;q21) IGH-MALT1 oncoprotein. Oncoproteins activate NFκB, Toll-like receptors TLR2 & TLR6, chemokine receptor CCR2, clusters of differentiation CD69 & Bcl2. In translocation-negative lymphoma: IL-8 production, CD28, CD86 expression, ICOS (inducible T-cell costimulator) activation	[735]
Dysregulated NFκB pathway	[736]
Helicobacter virulence gene/gene-product protein CagA: CagA translocates (is horizontally transferred) into gastric epithelial cells and into B lymphocytes. Recipient cells phosphorylate (activate) CagA protein. CagA activates ERK and Bcl-2/Bcl-XL anti-apoptotic proteins. CagA is an oncoprotein	[737a,b]
Helicobacter-reactive host immune T cells: Are armed with FasL (ligand) and perforin cross-react in an autoimmune fashion with host cell ATPase autoantigens, kill mucosal cells causing atrophy of gastric mucosa. Immune T cells mobilized against MALT lymphoma B cells are defective in FasL and perforin expression and fail to eradicate B lymphoma cells. In a murine model of Helicobacter-induced gastric lymphoma, CD4+CD25+FoxP3+ Treg cells were attracted into the tumor by chemokines CCL17/CCL22. The regulatory T cells eliminated immune T cells and promoted tumor growth	[738, 739]
Eradication of H. pylori: Antibiotics sensitive. Treatment results in lymphoma remission	[640, 740]
Commensal bacteria (Bacteroides vulgatus, Fusobacterium varium)
Commensal bacteria adhere to, and enter the cytoplasms of colonic epithelial cells. In response, the cells produce IL-6, IL-8, TNF-α, macrophage/monocyte chemoattractant protein-1. The intranuclear NFκB p65 is phosphorylated (activated). These reactions occur in UC cells in vitro and in vivo, as illustrated	[741]
Bacteroides fragilis enterotoxin activates the REL protein (vide supra) heterodimer, NFκB. In response, chemokine (CCL2, chemoattractant for monocytes; CXCL1, growth-related oncogene-α (GRO-α); CXCL8/IL-8) gene overexpression induce neutrophil transmigration	[742]
Comments: Not addressed in this article is the strong possibility that bacteroides enterotoxin-stimulated colonic epithelial cells express FasL, with which they kill Fas receptor-positive host immune T cells. It is well documented that FasL-expressing tumor cells attract granulocytic infiltrations. Genetically engineered immune T cells from patients with metastatic colon cancer express bispecific cytotoxicity to CEA+/CD3+ colon cancer cells	[743–754]