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2000
Volume 21, Issue 5
  • ISSN: 1573-3947
  • E-ISSN: 1875-6301

Abstract

Kaposi Sarcoma (KS) stems from malignant endothelial cells targeting the cutaneous and lymphatic systems. The aetiological agent, human herpesvirus type 8, has been implicated in the induction of KS. Of the four variants of KS that exist, HIV/AIDS associated KS remains one of the leading cancers in people living with HIV in sub-Saharan Africa (SSA). It is estimated that approximately 80% of KS cases were attributed to HIV in 2020. With the introduction of anti-retroviral therapy (ART) the burden of KS was temporarily alleviated. To date, its prevalence on the continent remains significant in comparison to the rest of the world. Traditional therapeutics such as chemotherapy continue to be the most common form of managing HIV-associated KS; however, the incidence of this global cancer continues to rise, predominantly in SSA. Furthermore, a significant number of HIV/AIDS-associated KS patients had been observed with normal CD4+ count and low viral load levels. This necessitates the development of other therapeutic strategies to collectively manage the continental crisis. Various strategies, such as immunomodulatory agents, monoclonal antibodies and therapeutic cytokines, are being investigated to be used as potential therapeutic strategies. One strategy highlights targeting the signalling pathways and growth factors involved in angiogenesis, which is an important characteristic of KS. The PD-1/PD-L1 immune checkpoint blockades are particularly interesting since cell cycle inhibitors have shown promising results as a potential immunotherapeutic agent. Predictive biomarkers and alternative vaccines will be discussed here while potential barriers which reduce the impact of immunotherapy are discussed throughout the review.

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2024-06-05
2026-02-13

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References

  1. CesarmanE. DamaniaB. KrownS.E. MartinJ. BowerM. WhitbyD. Kaposi sarcoma.Nat. Rev. Dis. Primers201951910.1038/s41572‑019‑0060‑9 30705286
     [Google Scholar]
  2. MaurerT. PonteM. LeslieK. HIV-associated Kaposi’s sarcoma with a high CD4 count and a low viral load.N. Engl. J. Med.2007357131352135310.1056/NEJMc070508 17898112
     [Google Scholar]
  3. RamaswamiR. PolizzottoM.N. LurainK. Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection.Clin. Cancer Res.202228584085010.1158/1078‑0432.CCR‑21‑3364 34862247
     [Google Scholar]
  4. SchwartzR.A. Kaposi’s sarcoma: An update.J. Surg. Oncol.200487314615110.1002/jso.20090 15334644
     [Google Scholar]
  5. SiegelJ.H. JanisR. AlperJ.C. SchutteH. RobbinsL. BlaufoxM.D. Disseminated visceral Kaposi’s sarcoma. Appearance after human renal homograft operation.JAMA196920781493149610.1001/jama.1969.03150210077009 4884743
     [Google Scholar]
  6. GottliebG.J. RagazA. VogelJ.V. A preliminary communication on extensively disseminated Kaposiʼs sarcoma in young homosexual men.Am. J. Dermatopathol.19813211111410.1097/00000372‑198100320‑00002 7270808
     [Google Scholar]
  7. DenisD. SetaV. RosencherR.E. A fifth subtype of Kaposi’s sarcoma, classic Kaposi’s sarcoma in men who have sex with men: A cohort study in Paris.J. Eur. Acad. Dermatol. Venereol.20183281377138410.1111/jdv.14831 29377280
     [Google Scholar]
  8. FerlayJ. ColombetM. SoerjomataramI. Cancer statistics for the year 2020: An overview.Int. J. Cancer2021149477878910.1002/ijc.33588 33818764
     [Google Scholar]
  9. ZeinatyP.E. LebbéC. DelyonJ. Endemic Kaposi’s Sarcoma.Cancers202315387210.3390/cancers15030872 36765830
     [Google Scholar]
  10. KhalilI.A. FranceschiS. de MartelC. BrayF. CliffordG.M. Burden of Kaposi sarcoma according to HIV status: A systematic review and global analysis.Int. J. Cancer2022150121948195710.1002/ijc.33951 35085400
     [Google Scholar]
  11. SitasF. ParkinD.M. ChirenjeM. Part II: Cancer in Indigenous Africans—causes and control.Lancet Oncol.20089878679510.1016/S1470‑2045(08)70198‑0 18672214
     [Google Scholar]
  12. GalaninaN. GoodmanA.M. CohenP.R. FramptonG.M. KurzrockR. Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade.Cancer Immunol. Res.20186101129113510.1158/2326‑6066.CIR‑18‑0121 30194084
     [Google Scholar]
  13. ChinulaL. MosesA. GopalS. HIV-associated malignancies in sub-Saharan Africa.Curr. Opin. HIV AIDS2017121899510.1097/COH.0000000000000329 27607593
     [Google Scholar]
  14. MosamA. ShaikF. UldrickT.S. A randomized controlled trial of highly active antiretroviral therapy versus highly active antiretroviral therapy and chemotherapy in therapy-naive patients with HIV-associated Kaposi sarcoma in South Africa.J. Acquir. Immune Defic. Syndr.201260215015710.1097/QAI.0b013e318251aedd 22395672
     [Google Scholar]
  15. RoystonL. IsnardS. CalmyA. RoutyJ.P. Kaposi sarcoma in antiretroviral therapy-treated people with HIV: A wake-up call for research on human herpesvirus-8.AIDS202135101695169910.1097/QAD.0000000000002933 33966030
     [Google Scholar]
  16. NgalamikaO. TsoF.Y. LidengeS. Outcome markers of ART-treated HIV+ patients with early stage Kaposi’s sarcoma.PLoS One2020157e023586510.1371/journal.pone.0235865 32634155
     [Google Scholar]
  17. LidengeS.J. TsoF.Y. NgalamikaO. Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors.Oncotarget202011171556157210.18632/oncotarget.27569 32391124
     [Google Scholar]
  18. JaryA. LeducqV. DesireN. New Kaposi’s sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies.J. Infect. Dis.202022281320132810.1093/infdis/jiaa180 32282911
     [Google Scholar]
  19. PalichR. VeyriM. ValantinM.A. Recurrence and Occurrence of Kaposi’s Sarcoma in Patients Living With Human Immunodeficiency Virus (HIV) and on Antiretroviral Therapy, Despite Suppressed HIV Viremia.Clin. Infect. Dis.202070112435243810.1093/cid/ciz762 31626689
     [Google Scholar]
  20. MartinP.I. RoguetO.V. DuvivierC. Kaposi sarcoma among people living with HIV in the French DAT ’ AIDS cohort between 2010 and 2015.J. Eur. Acad. Dermatol. Venereol.20203451065107310.1111/jdv.16204 31953902
     [Google Scholar]
  21. SéverinD. BessaoudF. MeftahN. A comparative study of classic and HIV-viremic and aviremic AIDS Kaposi sarcoma.AIDS202135339940510.1097/QAD.0000000000002744 33181532
     [Google Scholar]
  22. BellonM. NicotC. Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection.Viruses201791028910.3390/v9100289 28981470
     [Google Scholar]
  23. TulpuleA. ScaddenD.T. EspinaB.M. Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi’s sarcoma.J. Clin. Oncol.200018471672310.1200/JCO.2000.18.4.716 10673512
     [Google Scholar]
  24. FardhdianiV. MolfinoL. ZamudioA.G. HIV-associated Kaposi’s sarcoma in Maputo, Mozambique: Outcomes in a specialized treatment center, 2010–2015.Infect. Agent. Cancer2018131510.1186/s13027‑018‑0177‑6 29387144
     [Google Scholar]
  25. CooleyT. HenryD. TondaM. SunS. O’ConnellM. RackoffW. A randomized, double-blind study of pegylated liposomal doxorubicin for the treatment of AIDS-related Kaposi’s sarcoma.Oncologist200712111412310.1634/theoncologist.12‑1‑114 17227906
     [Google Scholar]
  26. KrownS.E. MoserC.B. MacPhailP. Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: A three-arm, open-label, randomised, non-inferiority trial.Lancet2020395102311195120710.1016/S0140‑6736(19)33222‑2 32145827
     [Google Scholar]
  27. LiewY.C.C. TamY.C.S. OhC.C. Treatments for AIDS/HIV‐related Kaposi sarcoma: A systematic review of the literature.Int. J. Dermatol.202261111311132410.1111/ijd.16318 35775738
     [Google Scholar]
  28. GoffC.B. DasanuC.A. Changing therapeutic landscape in advanced Kaposi sarcoma: Current state and future directions.J. Oncol. Pharm. Pract.202329491792610.1177/10781552221148417 36718515
     [Google Scholar]
  29. RamaswamiR. LurainK. YarchoanR. Oncologic Treatment of HIV-Associated Kaposi Sarcoma 40 Years on.J. Clin. Oncol.202240329430610.1200/JCO.21.02040 34890242
     [Google Scholar]
  30. PurushothamanP. UppalT. SarkarR. VermaS. KSHV-Mediated Angiogenesis in Tumor Progression.Viruses20168719810.3390/v8070198 27447661
     [Google Scholar]
  31. UldrickT.S. WyvillK.M. KumarP. Phase II study of bevacizumab in patients with HIV-associated Kaposi’s sarcoma receiving antiretroviral therapy.J. Clin. Oncol.201230131476148310.1200/JCO.2011.39.6853 22430271
     [Google Scholar]
  32. LeungD.W. CachianesG. KuangW.J. GoeddelD.V. FerraraN. Vascular endothelial growth factor is a secreted angiogenic mitogen.Science198924649351306130910.1126/science.2479986 2479986
     [Google Scholar]
  33. UldrickT.S. GonçalvesP.H. WyvillK.M. A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma.Oncologist2017225505e4910.1634/theoncologist.2016‑0486 28341759
     [Google Scholar]
  34. JaysonG.C. KerbelR. EllisL.M. HarrisA.L. Antiangiogenic therapy in oncology: Current status and future directions.Lancet20163881004351852910.1016/S0140‑6736(15)01088‑0 26853587
     [Google Scholar]
  35. BarenholzY.C. Doxil® — The first FDA-approved nano-drug: Lessons learned.J. Control. Release2012160211713410.1016/j.jconrel.2012.03.020 22484195
     [Google Scholar]
  36. SantarelliR. GonnellaR. Di GiovenaleG. STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells.Sci. Rep.201441424110.1038/srep04241 24577500
     [Google Scholar]
  37. ShielsM.S. PfeifferR.M. HallH.I. Proportions of Kaposi sarcoma, selected non-Hodgkin lymphomas, and cervical cancer in the United States occurring in persons with AIDS, 1980-2007.JAMA2011305141450145910.1001/jama.2011.396 21486978
     [Google Scholar]
  38. ReidE.G. SuazoA. LensingS.Y. Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.Clin. Cancer Res.202026355856510.1158/1078‑0432.CCR‑19‑1044 31624104
     [Google Scholar]
  39. ChangV.A. WangH.Y. ReidE.G. Activity of brentuximab vedotin in AIDS-related primary effusion lymphoma.Blood Adv.20193576676810.1182/bloodadvances.2018026351 30837213
     [Google Scholar]
  40. RamaswamiR. LurainK. PeerC.J. Tocilizumab in patients with symptomatic Kaposi sarcoma herpesvirus–associated multicentric Castleman disease.Blood2020135252316231910.1182/blood.2019004602 32276276
     [Google Scholar]
  41. KrownS.E. LiP. Von RoennJ.H. ParedesJ. HuangJ. TestaM.A. Efficacy of low-dose interferon with antiretroviral therapy in Kaposi’s sarcoma: A randomized phase II AIDS clinical trials group study.J. Interferon Cytokine Res.200222329530310.1089/107999002753675712 12034036
     [Google Scholar]
  42. PuronenC.E. FordE.S. UldrickT.S. Immunotherapy in People With HIV and Cancer.Front. Immunol.201910206010.3389/fimmu.2019.02060 31555284
     [Google Scholar]
  43. SteidlC. LeeT. ShahS.P. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma.N. Engl. J. Med.20103621087588510.1056/NEJMoa0905680 20220182
     [Google Scholar]
  44. FreemanG.J. LongA.J. IwaiY. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.J. Exp. Med.200019271027103410.1084/jem.192.7.1027 11015443
     [Google Scholar]
  45. TopalianS.L. HodiF.S. BrahmerJ.R. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.N. Engl. J. Med.2012366262443245410.1056/NEJMoa1200690 22658127
     [Google Scholar]
  46. DriscollC.B. SchuelkeM.R. KottkeT. APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy.Nat. Commun.202011179010.1038/s41467‑020‑14568‑7 32034147
     [Google Scholar]
  47. CoronaS.P. GeneraliD. Abemaciclib: A CDK4/6 inhibitor for the treatment of HR+/HER2– advanced breast cancer.Drug Des. Devel. Ther.20181232133010.2147/DDDT.S137783 29497278
     [Google Scholar]
  48. A Phase I/II Study of Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma.Available from: https://www.medifind.com/articles/clinical-trial/310065901 [Cited on: 2024 Feb 14].
  49. RemleyV.A. LindenJ. BauerT.W. DimastromatteoJ. Unlocking antitumor immunity with adenosine receptor blockers.Cancer Drug Resist.20236474876710.20517/cdr.2023.63 38263981
     [Google Scholar]
  50. VijayanD. YoungA. TengM.W.L. SmythM.J. Erratum: Targeting immunosuppressive adenosine in cancer.Nat. Rev. Cancer2017171276510.1038/nrc.2017.110 29162946
     [Google Scholar]
  51. SunC. WangB. HaoS. Adenosine-A2A Receptor Pathway in Cancer Immunotherapy.Front. Immunol.20221383723010.3389/fimmu.2022.837230 35386701
     [Google Scholar]
  52. AllardB. AllardD. BuisseretL. StaggJ. The adenosine pathway in immuno-oncology.Nat. Rev. Clin. Oncol.2020171061162910.1038/s41571‑020‑0382‑2 32514148
     [Google Scholar]
  53. FongL. HotsonA. PowderlyJ.D. Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer.Cancer Discov.2020101405310.1158/2159‑8290.CD‑19‑0980 31732494
     [Google Scholar]
  54. WHO | Regional Office for Africa [Internet]Preventing and Responding to HIV Drug Resistance in the African Region: Regional action plan 2019-2023.Available from: https://www.afro.who.int/publications/preventing-and-responding-hiv-drug-resistance-african-region-regional-action-plan-2019 [Cited on: 2023 Oct 24].2023
  55. GuihotA. DupinN. MarcelinA.G. Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma.J. Infect. Dis.200619481078108810.1086/507648 16991082
     [Google Scholar]
  56. CasperC. CoreyL. CohenJ.I. DamaniaB. GershonA.A. KaslowD.C. KSHV (HHV8) vaccine: Promises and potential pitfalls for a new anti-cancer vaccine. npj.Vaccines202271110 36679846
     [Google Scholar]
  57. NalwogaA. RoshanR. MooreK. Kaposi’s sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda.Nat. Commun.2021121732310.1038/s41467‑021‑27623‑8 34916520
     [Google Scholar]
  58. GibneyG.T. WeinerL.M. AtkinsM.B. Predictive biomarkers for checkpoint inhibitor-based immunotherapy.Lancet Oncol.20161712e542e55110.1016/S1470‑2045(16)30406‑5 27924752
     [Google Scholar]
  59. TessemaZ.T. WorkuM.G. TesemaG.A. Determinants of accessing healthcare in Sub-Saharan Africa: A mixed-effect analysis of recent Demographic and Health Surveys from 36 countries.BMJ Open2022121e05439710.1136/bmjopen‑2021‑054397 35105635
     [Google Scholar]
  60. MamimandjiamiA.I. OndéméM.A. RamassamyJ.L. Epidemiology and Genetic Variability of HHV-8/KSHV among Rural Populations and Kaposi’s Sarcoma Patients in Gabon, Central Africa. Review of the Geographical Distribution of HHV-8 K1 Genotypes in Africa.Viruses202113217510.3390/v13020175 33503816
     [Google Scholar]
/content/journals/cctr/10.2174/0115733947296874240524074647
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Immunotherapy in HIV-associated Kaposi Sarcoma: Challenges and Prospects
Curr Cancer Ther Rev 21, 645 (2025); https://doi.org/10.2174/0115733947296874240524074647
/content/journals/cctr/10.2174/0115733947296874240524074647
/content/journals/cctr/10.2174/0115733947296874240524074647
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  • Article Type:     Review Article
Keyword(s): anti-retroviral therapy (ART); biomarkers; cancer immunotherapy; HIV/AIDS-associated KS; human gamma herpesvirus 8 (HHV-8); immune checkpoint blockades; Kaposi Sarcoma; KS in sub-Saharan Africa

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