Immune Dysfunction and the Pathogenesis of AIDS-associated non-Hodgkin's Lymphoma

Abstract

Much has been learned about how HIV-induced immune dysfunction

Elevated Serum Soluble CD30 Precedes the Development of AIDS-Associated Non-Hodgkin’s B Cell Lymphoma

“…This is the fi rst report of elevated sCD30 in subjects who developed AIDS-NHL, and to our knowledge, the fi rst to examine sCD30 in serum samples obtained prior to the diagnosis of any type of B cell lymphoma ( fi g. 1 ). Unlike CD30-positive HL, where elevated circulating levels of sCD30 at diagnosis would likely refl ect the shedding of surface CD30 from tumor cells, we suggest that our observation of elevated sCD30 in prelymphoma sera from AIDS-NHL cases is indicative of the type of immune system hyperactivation that is thought to contribute to the process of B cell lymphomagenesis [8,9] . The elevated sCD30 levels seen in the subjects who went on to develop lymphoma are likely the products of cell surface CD30 expression not only by increased numbers of activated B cells (the potentially malignant cells), but also by activated type 2 T cells that secrete B cell-stimulatory cytokines, thereby creating and/or sustaining an environment that would facilitate the development of a B cell tumor [1][2][3] .…”

“…Sustained B cell stimulation in such an environment leads to increased immunoglobulin class switching and somatic hypermutation, DNA-modifying activities that increase the risk of genetic changes implicated in B cell lymphomagenesis [8,9] . While sCD30 itself may not be driving lymphomagenesis, our observation of elevated levels of serum sCD30 prior to the clinical diagnosis of NHL suggests that it could be an important biomarker for the appropriate conditions which facilitate the establishment and/or growth of this kind of B cell tumor.…”

“…In particular, because CD30 is expressed on both activated B cells and the type 2 subset of T cells that secrete B cellstimulatory cytokines, increases in serum sCD30 would be an indicator of both increased B cell activation and an immune environment conducive to chronic B cell stimulation. Since B cell NHL is thought to arise as a result of inappropriate and/or excessive B cell activation [8,9] , serum sCD30 is an attractive candidate as a possible precancer marker for the development of NHL. This may be particularly true among NHL associated with HIV infection and acquired immunodefi ciency syndrome (AIDS-NHL), nearly all of which are CD30-negative B cell tumors thought to be driven, at least in part, by B cell dysregulation and/or hyperactivation [1,8,9] .…”

“…Since B cell NHL is thought to arise as a result of inappropriate and/or excessive B cell activation [8,9] , serum sCD30 is an attractive candidate as a possible precancer marker for the development of NHL. This may be particularly true among NHL associated with HIV infection and acquired immunodefi ciency syndrome (AIDS-NHL), nearly all of which are CD30-negative B cell tumors thought to be driven, at least in part, by B cell dysregulation and/or hyperactivation [1,8,9] . It is a challenge to evaluate possible precancer markers, as the availability of clinical materials that have been collected prior to the diagnosis of cancer is limited.…”

Changes in the Activation and Reconstitution of Lymphocytes Resulting from Total-Body Irradiation Correlate with Slowed Tumor Growth

“…Although natural killer (NK) cells have traditionally been considered the cells primarily involved in immune surveillance, the tumoricidal properties of T lymphocytes, monocytes-macrophages, and neutrophils have also been demonstrated [10, 11, 12, 13]. The observation that immunocompromised individuals are predisposed to enhanced tumor incidence and progression lends credence to the conclusion that the collective tumor destruction waged by these cells is substantial [14]. While it is known that lymphoid cells and organs are extremely susceptible to the effects of ionizing radiation, different cell types display varying degrees of radiosensitivity [15, 16].…”