74 © 2019 Journal of Immunotherapy and Precision Oncology | Published by Wolters Kluwer - Medknow Introduction Kaposi’s sarcoma (KS) is caused by infection with KS herpesvirus (KSHV), also known as human herpesvirus‑8 (HHV‑8), a linear, double‑stranded enveloped DNA virus, with its effect mainly seen on endothelial cells. It presents most commonly with skin lesions described as purple, brown, and red patches that progress to plaques to nodules. There are four commonly described subtypes of KS. The classic (sporadic) form is most prevalent in males over the age of 50 of European or Mediterranean descent that usually presents on the lower extremities. The endemic or African form is seen in sub‑Saharan Africa, mostly in children suffering from chronic illness with substantial similarity to HIV‑associated KS. [1] The iatrogenic form is seen in patients on immunosuppressive drug therapy, typically transplant patients, again with similarities to endemic and HIV‑associated KS. Finally, the epidemic form or AIDS‑related KS is predominant in men who have sex with men (MSM) and arose after the HIV/AIDS epidemic Address for correspondence: Dr. Omar Pacha, MD Anderson Cancer Center, 1400 Pressler Street, Unit 1452, Houston, TX 77030, USA. E‑mail: OPacha@mdanderson. org Abstract Kaposi’s sarcoma (KS) is a virally induced tumor most commonly appearing in the immunosuppressed. It is caused by infection with human herpesvirus‑8, which in healthy individuals causes no symptoms. However, in patients with weakened immune systems, such as in HIV and organ transplant patients, the virus can proliferate leading to KS. Following the introduction of antiretroviral therapy (ART) for HIV and AIDS, the prevalence of AIDS‑related KS has fallen, but it has begun to appear in subsets of patients on treatment. Treatments for KS vary depending on the cause of immunosuppression. In the case of HIV, ART is the frst‑line treatment, but other therapies are initiated based on tumor response. In transplant patients, primary treatment involves stopping or reducing immunosuppression and similarly advancing to other therapies based on response. This presents a dilemma in many cases where chemotherapy will reduce an already‑weakened immune system or in strengthening an immune system in patients at risk for transplant rejection. This review will focus on summarizing the effects of immunosuppression in HIV‑related (epidemic) and iatrogenically immunosuppressed transplant patients with KS and its etiology, pathophysiology, current treatments, and management along with novel therapies. Keywords: AIDS‑related Kaposi sarcoma, Kaposi sarcoma, Kaposi sarcoma in HIV patients, Kaposi sarcoma in immunocompromised patients Kaposi’s Sarcoma in the Immunosuppressed Review Article Nisha A Reddy, Steven R Mays, Omar Pacha Department of Dermatology, MD Anderson Cancer Center Houston, Medical School Houston, Houston, TX, USA This is an open access journal, and artcles are distributed under the terms of the Creatve Commons Atributon‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creatons are licensed under the identcal terms. For reprints contact: reprints@medknow.com in 1980. [2,3] KS has also been increasingly seen in a potential ffth patient subgroup containing MSM that are HIV seronegative with no identifable immunodefciency. [4] Etiology and Transmission of Kaposi’s Sarcoma KS is caused by HHV‑8/KSHV which is found in all those who are affected. [5] HHV‑8 interferes with normal cellular function by invading and remaining latent inside the cells until switched to the lytic stage. Viral infection activates mammalian target of rapamycin (mTOR), thereby initiating mesenchymal differentiation and subsequent angiogenesis. [2] It can maintain this through immunosuppression using the latency‑associated nuclear antigen (LANA), an oncogenic protein that dysregulates various tumor suppressor pathways such as pRb and p53. It also blocks the expression of reactivation transcriptional activator thereby preventing lysis. [6] It is mainly transmitted in the general population during childhood via saliva but can also be transmitted sexually, through blood transfusions, and by intravenous drug use. [7] Seroprevalence of the general population Access this article online Website: www.jipoonline.org DOI: 10.4103/JIPO.JIPO_10_19 Quick Response Code: How to cite this article: Reddy NA, Mays SR, Pacha O. Kaposi's sarcoma in the immunosuppressed. J Immunother Precis Oncol 2019;2:74-8. Received: April 18, 2019 Accepted: May 24, 2019 Published: June 28, 2019 [Downloaded free from http://www.jipoonline.org on Thursday, February 13, 2020, IP: 10.232.74.22]