<scp>PD</scp>‐1 and <scp>PD‐L1</scp> expression in Kaposi sarcoma: A comparative study according to the pathological stage and clinical characteristics

Since the advent of highly effective combined antiretroviral treatment (cART), and with the implementation of large HIV testing programs and universal access to cART, the burden of AIDS-related comorbidities has dramatically decreased over time. The incidence of Kaposi’s sarcoma (SK), strongly associated with HIV replication and CD4 immunosuppression, was greatly reduced. However, KS remains the most common cancer in patients living with HIV (PLHIV). HIV physicians are increasingly faced with KS in virally suppressed HIV-patients, as reflected by increasing description of case series. Though SK seem less aggressive than those in PLHIV with uncontrolled HIV-disease, some may require systemic chemotherapy. Persistent lack of specific anti-HHV-8 cellular immunity could be involved in the physiopathology of these KS. These clinical forms are a real therapeutic challenge without possible short-term improvement of anti-HHV-8 immunity, and no active replication of HIV to control. The cumulative toxicity of chemotherapies repeatedly leads to a therapeutic dead end. The introduction or maintenance of protease inhibitors in cART does not seem to have an impact on the evolution of these KS. Research programs in this emerging condition are important to consider new strategies.

Section: Therapeutic Challenges For Treating Ks In Virally Suppressed Hiv-patientsmentioning

confidence: 94%

Kaposi’s Sarcoma in Virally Suppressed People Living with HIV: An Emerging Condition

Palich

Makinson

Veyri

et al. 2021

“…Blocking immune checkpoints could restore anti-HHV-8 immunity and help control the tumor process. On the other hand, PD-1 and PD-L1 expression within the tumor tissue, which has been shown to be strongly correlated with the efficacy of immunotherapy [106], has been reported in KS biopsies [107][108][109][110][111][112]. Of note, other biomarkers, such as tumor-infiltrating lymphocytes, mutational burden, or immune gene signatures, may be associated with the response to therapy and have not been studied in KS [106].…”

Section: Immunotherapies In Ks Treatmentmentioning

confidence: 99%

Therapeutic Perspectives in the Systemic Treatment of Kaposi’s Sarcoma

Valantin

Royston

Hentzien³

et al. 2022

In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

“…Over the past few years, several studies have therefore been carried out to investigate the prognostic value of programmed death-1 (PD-1)/PD-ligand-1 (PD-L1) expression in KS with controversial results and a lack of standardized protocols for PD-L1 detection [ 16 , 17 , 18 , 19 ]. The most recent studies, focusing on PD-L1 expression in the different cell populations, found a pathological-stage-related increase of PD-L1 expression in the tumor microenvironment [ 20 , 21 , 22 ]. These results provide the rationale for the clinical development of checkpoint inhibitors targeting PD-1/PD-L1 in refractory KS, but further clinical and molecular studies in large patient groups are needed, as well as standardization of PD-L1 testing.…”

Section: Histopathological Characteristicsmentioning

confidence: 99%

Current and Future Tools for Diagnosis of Kaposi’s Sarcoma

Dupin

Jary

Boussouar

et al. 2021

Kaposi’s sarcoma (KS) is a rare, atypical malignancy associated with immunosuppression and can be qualified as an opportunistic tumor, which responds to immune modulation or restoration. Four different epidemiological forms have been individualized (AIDS-related, iatrogenic, endemic or classic KS). Although clinical examination is sufficient to diagnose cutaneous lesions of KS, additional explorations are necessary in order to detect lesions involving other organs. New histological markers have been developed in recent years concerning the detection of HHV-8 latent or lytic proteins in the lesions, helping to confirm the diagnosis when it is clinically doubtful. More recently, the evaluation of the local immune response has also been shown to provide some guidance in choosing the appropriate therapeutic option when necessary. We also review the indication and the results of conventional radiological imaging and of non-invasive imaging tools such as 18F-fluoro-deoxy-glucose positron emission tomography, thermography and laser Doppler imaging for the diagnosis of KS and for the follow-up of therapeutic response in patients requiring systemic treatment.