Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

Abstract

The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of aVb3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in aVb3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of aVb3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

Engineering Human Tumor-specific Cytotoxic T Cells to Function in a Hypoxic Environment

“…This modification restores T-cell expansion under hypoxic conditions in vitro and augments tumor infiltration even in areas of hypoxia in vivo. [1][2][3][4][5][6][7][8] In the great majority of studies, T cells utilized for cancer immunotherapy are grown and stimulated in vitro to generate CTL with optimal phenotype and function at 20% oxygen. These conditions, however, are not representative of those that are present at many sites of human tumors, in which oxygen tension is variable and is often significantly lower.…”

“…[1][2][3][4][5][6][7][8] This phenomenon is usually due to inadequate neo-vasculature in a rapidly growing malignancy, increased vascular permeability (producing hemoconcentration and high interstitial pressure), and/or anemia 9 (from the disease or its treatment). Hypoxic areas of tumors are often resistant to chemo-radiotherapy, because locally deficient drug biodistribution and altered cellular metabolism may reduce the effectiveness of these agents.…”

Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment

“…Distinction was made between interfollicular vessels and those within neoplastic follicles based on the characteristic vascular distribution in FL. 18 The software generated vessel numbers and vessel size and allowed further analysis restricted to a defined vessel area. Macrophage density was assessed by absolute macrophage number using image analysis and scored semiquantitatively based on cells/high power field by 2 pathologists (M.C., A.M.L.).…”

Vascular endothelial growth factor expression in low and high grade b-cell non-hodgkin's lymphomas

“…A dominant angiogenic factor may still induce angiogenesis in vivo in any tumor (25). The interplay between lymphoma cells and tumor vessels is complex (26). It is therefore difficult to determine which angiogenic factor could lead to angiogenesis and tumor progression in NHL.…”