PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?

Lavolé, A.; Guihot, Amélie; Veyri, Marianne; Lambotte, Olivier; Autran, Brigitte; Cloarec, Nicolas; Garff, G. Le; Flament, Thomas; Cadranel, J.; Spano, Jean‐Philippe

doi:10.1093/annonc/mdx817

Cited by 32 publications

(11 citation statements)

References 5 publications

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“…A prospective cohort study of 10 PLWH with NSCLC treated with nivolumab noted similar response rates to HIV-uninfected patients: 2 patients had a partial response, 4 had stable disease, and 4 progressed. All patients tolerated nivolumab well with no serious adverse events (70). A prospective phase 1 study of pembrolizumab in PLWH with a CD4 count >100 cells/μl and advanced cancer demonstrated evidence of safety and activity in KS, NHL, lung cancer, and liver cancer (118).…”

Section: Antiretroviral Therapy and Other Forms Of Immunotherapy In Hmentioning

confidence: 89%

Immunotherapy in People With HIV and Cancer

2019

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HIV infection alters the natural history of several cancers, in large part due to its effect on the immune system. Immune function in people living with HIV may vary from normal to highly dysfunctional and is largely dependent on the timing of initiation (and continuation) of effective antiretroviral therapy (ART). An individual's level of immune function in turn affects their cancer risk, management, and outcomes. HIV-associated lymphocytopenia and immune dysregulation permit immune evasion of oncogenic viruses and premalignant lesions and are associated with inferior outcomes in people with established cancers. Various types of immunotherapy, including monoclonal antibodies, interferon, cytokines, immunomodulatory drugs, allogeneic hematopoietic stem cell transplant, and most importantly ART have shown efficacy in HIV-related cancer. Emerging data suggest that checkpoint inhibitors targeting the PD-1/PD-L1 pathway can be safe and effective in people with HIV and cancer. Furthermore, some cancer immunotherapies may also affect HIV persistence by influencing HIV latency and HIV-specific immunity. Studying immunotherapy in people with HIV and cancer will advance clinical care of all people living with HIV and presents a unique opportunity to gain insight into mechanisms for HIV eradication.

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Section: Antiretroviral Therapy and Other Forms Of Immunotherapy In Hmentioning

confidence: 89%

Immunotherapy in People With HIV and Cancer

2019

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“…In the case of nivolumab, the study was conducted only on one patient who experienced a drastic and sustained decrease of the HIV-1 reservoir . However, other controversial studies found no consistent changes in the size of the latent reservoir nor in HIV-specific CD8 + T-cell responses in HIV-1infected individuals treated with anti-PD1 antibodies (including nivolumab) (Le Garff et al, 2017;Evans et al, 2018;Lavolé et al, 2018;Scully et al, 2018). Success to completely eradicate latent viruses with LRAs is hampered by the heterogeneous nature of the latent reservoir and by the diversity of the silencing mechanisms governing latency that make the current "shock and kill" strategy inefficient.…”

Section: Shock and Kill Strategy To Eliminate The Latent Reservoirmentioning

confidence: 99%

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Aït-Ammar

Kula

Darcis³

et al. 2020

Front. Microbiol.

131

150

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Quantitative polymerase chain reaction; QVOA, quantitative viral outgrowth assays; Rev, regulator of virion expression; RNA, ribonucleic acid; RNAPII, RNA polymerase II; RT-ddPCR, teverse transcription droplet digital PCR; SAHA, suberoylanilide hydroxamic acid; SIV, simian immunodeficiency virus; SMAC, second mitochondrial activator of caspases; SMYD2, SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing protein 2; Sp1, specificity protein 1; STAT5, signal transducer and activator of transcription 5; Suv39H1, Suppressor of variegation 3-9 homolog 1

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“…Conversely, a recent study analyzed data obtained from HIV-infected patients receiving treatment for NSCLC with a PD-1 blocker and came to different conclusions. Lavolé et al ( 44 ) showed that both the proviral load and CD4 + T cell counts remained stable in patients receiving multiple doses of nivolumab, suggesting the drug does not function as an LRA as efficiently as previously thought ( 44 ). Furthermore, a second study found no consistent changes in either virological or immunological status in HIV-infected participants treated for malignancy with PD-1 blockers ( 45 ).…”

Section: Immune Checkpoint Inhibitors and Hiv Infectionmentioning

confidence: 94%

Targeting Immune Checkpoint Molecules to Eliminate Latent HIV

Boyer

Palmer

2018

Front. Immunol.

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The advent of antiretroviral therapy (ART) has seen a dramatic decrease in the morbidity and mortality of individuals infected with human immunodeficiency virus (HIV). However, ART is not curative and HIV persists in treated individuals within a pool of infected CD4+ memory T cells. The targeting and elimination of these cells, termed the latent HIV reservoir, may be essential in establishing a cure for HIV. Current HIV reservoir research is focused on identifying cells that harbor latent, replication-competent, HIV provirus using specific cell surface markers. Recently, studies have turned to immune checkpoint (IC) molecules, such as programmed cell death protein 1 (PD-1). IC molecules are regulators of the immune system and have previously been linked to HIV infection. Furthermore, cells isolated from treated individuals co-expressing PD-1 alongside other IC molecules are enriched for HIV DNA. Administration of a IC blocking antibodies resulted in an increase of cell-associated HIV RNA within an individual, indicating the potential for this therapeutic to be utilized as a latency reversing agent. IC inhibitors could target CD4+ T cells expressing IC molecules and possibly enhance HIV transcription, allowing for the elimination of these cells by either ART or the immune system. However, treatment with IC inhibitors has been associated with toxicities such as immune-related adverse events and therefore future studies should proceed with caution.

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PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?

Cited by 32 publications

References 5 publications

Immunotherapy in People With HIV and Cancer

Immunotherapy in People With HIV and Cancer

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Targeting Immune Checkpoint Molecules to Eliminate Latent HIV

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