AIDS-related malignancies: changing epidemiology and the impact of highly active antiretroviral therapy.
ABSTRACT Three cancers in people with HIV denote an AIDS diagnosis: Kaposi's sarcoma, high-grade B-cell non-Hodgkin's lymphoma and invasive cervical cancer. In addition a number of other cancers occur at increased frequency in this population group but are not AIDS-defining illnesses. This review discusses the impact of highly active antiretroviral therapy on the epidemiology and outcome of AIDS-defining cancers.
The incidence of both Kaposi's sarcoma and non-Hodgkin's lymphoma has declined in the era of highly active antiretroviral therapy and the outcome of both tumours has improved. Moreover, highly active antiretroviral therapy alone produces a response in a majority of antiretroviral-naïve patients with Kaposi's sarcoma. In contrast, highly active antiretroviral therapy has had little impact on the incidence of human papilloma virus-associated tumours (cervical and anal cancer) in people with HIV, although it may improve survival by reducing opportunistic infection deaths. As people with HIV live longer with highly active antiretroviral therapy, an increased incidence of other non AIDS-defining cancers that have no known association with oncogenic infections is becoming apparent.
For those with access to highly active antiretroviral therapy, the good news from the AIDS-defining cancers - particularly Kaposi's sarcoma and non-Hodgkin's lymphoma - may be balanced by the increasing numbers of non AIDS-defining cancers.
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ABSTRACT: Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation. Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow straight into overt tumors. These criteria would be fulfilled by CSCs. Stem cells are pluripotent, immune-privileged, and long-living, but depend on specialized niches. Thus, latent tumors may be maintained by a niche-constrained reservoir of long-living CSCs that are exempt from immunosurveillance while niche-independent and more immunogenic daughter cells are constantly eliminated. The small subpopulation of CSCs is often held responsible for tumor initiation, metastasis, and recurrence. Experimentally, this hypothesis was supported by the observation that only this subset can propagate tumors in non-obese diabetic/scid mice, which lack T and B cells. Yet, the concept was challenged when an unexpectedly large proportion of melanoma cells were found to be capable of seeding complex tumors in mice which further lack NK cells. Moreover, the link between stem cell-like properties and tumorigenicity was not sustained in these highly immunodeficient animals. In humans, however, tumor-propagating cells must also escape from immune-mediated destruction. The ability to persist and to initiate neoplastic growth in the presence of immunosurveillance - which would be lost in a maximally immunodeficient animal model - could hence be a decisive criterion for CSCs. Consequently, integrating scientific insight from stem cell biology and tumor immunology to build a new concept of "CSC immunology" may help to reconcile the outlined contradictions and to improve our understanding of tumorigenesis.Frontiers in Immunology 01/2014; 5:360.
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ABSTRACT: press as: Cobucci RNO, et al. Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: A systematic review. J Infect Public Health (2014),Journal of Infection and Public Health 10/2014;
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ABSTRACT: A high density of intratumoral effector memory CD8+/Th1 T cells is associated with favorable prognosis in most cancers and may be induced or increased by immunotherapy. Efficient adaptive immune reactions are shaped in tumor adjacent tertiary lymphoid structures, which exhibit all characteristics of immunity generating lymphoid formations in reactive lymph nodes. Malignant tumor cells impact favorably or deleteriously their immune microenvironment if they bear genetic mutations that result in neo-antigens or by producing chemokines and cytokines that recruit lymphocytes and myeloid cells or increase inflammation and neo-angiogenesis. This intricate network of interactions results in control or escape of tumors, and its understanding will help define goals to monitor efficiency of immunotherapies.Cancer Immunology and Immunotherapy 08/2014; · 3.94 Impact Factor