Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV
The pathogenesis of HIV immunodeficiency is mainly dependent on the cytopatic effects exerted by the virus against infected CD4+ T cells. However, CD4+ T cell loss cannot be the only pathogenic factor since severe opportunistic infections may develop in HIV infected patients with normal CD4+ T cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02447/full |
| _version_ | 1818909603034824704 |
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| author | Gilberto Filaci Gilberto Filaci Daniela Fenoglio Daniela Fenoglio Lucia Taramasso Francesco Indiveri Antonio Di Biagio |
| author_facet | Gilberto Filaci Gilberto Filaci Daniela Fenoglio Daniela Fenoglio Lucia Taramasso Francesco Indiveri Antonio Di Biagio |
| author_sort | Gilberto Filaci |
| collection | DOAJ |
| description | The pathogenesis of HIV immunodeficiency is mainly dependent on the cytopatic effects exerted by the virus against infected CD4+ T cells. However, CD4+ T cell loss cannot be the only pathogenic factor since severe opportunistic infections may develop in HIV infected patients with normal CD4+ T cell counts and since the recent START study indicated that absolute CD4+ T cell counts are not predictive for AIDS and non-AIDS events. Recently our group demonstrated that CD8+CD28-CD127lowCD39+ regulatory T lymphocytes, previously found highly concentrated within tumor microenvironment, circulate with elevated frequency in the peripheral blood of HIV infected patients. Here, we show that these cells, that at least in part are HIV specific, express the PD1 immune checkpoint. Based on these evidences and considerations, in this Perspective article we speculate on the opportunity to treat HIV infected patients with anti-PD1 immune checkpoint inhibitors as a way to counteract the T regulatory cell compartment and to unleash virus-specific immune responses. In order to potentiate the immune responses against HIV we also propose the potential utility to associate immune checkpoint inhibition with HIV-specific therapeutic vaccination, reminiscent of what currently applied in oncologic protocols. We suggest that such an innovative strategy could permit drug-sparing regimens and, perhaps, lead to eradication of the infection in some patients. |
| first_indexed | 2024-12-19T22:29:32Z |
| format | Article |
| id | doaj.art-06776e134f774e9db2461bbea79f5246 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T22:29:32Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-06776e134f774e9db2461bbea79f52462022-12-21T20:03:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02447408818Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIVGilberto Filaci0Gilberto Filaci1Daniela Fenoglio2Daniela Fenoglio3Lucia Taramasso4Francesco Indiveri5Antonio Di Biagio6Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Genoa, ItalyBiotherapy Unit, Ospedale Policlinico San Martino, Genoa, ItalyCentre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Genoa, ItalyBiotherapy Unit, Ospedale Policlinico San Martino, Genoa, ItalyInfectious Disease Unit, Ospedale Policlinico San Martino, Genoa, ItalyCentre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Genoa, ItalyInfectious Disease Unit, Ospedale Policlinico San Martino, Genoa, ItalyThe pathogenesis of HIV immunodeficiency is mainly dependent on the cytopatic effects exerted by the virus against infected CD4+ T cells. However, CD4+ T cell loss cannot be the only pathogenic factor since severe opportunistic infections may develop in HIV infected patients with normal CD4+ T cell counts and since the recent START study indicated that absolute CD4+ T cell counts are not predictive for AIDS and non-AIDS events. Recently our group demonstrated that CD8+CD28-CD127lowCD39+ regulatory T lymphocytes, previously found highly concentrated within tumor microenvironment, circulate with elevated frequency in the peripheral blood of HIV infected patients. Here, we show that these cells, that at least in part are HIV specific, express the PD1 immune checkpoint. Based on these evidences and considerations, in this Perspective article we speculate on the opportunity to treat HIV infected patients with anti-PD1 immune checkpoint inhibitors as a way to counteract the T regulatory cell compartment and to unleash virus-specific immune responses. In order to potentiate the immune responses against HIV we also propose the potential utility to associate immune checkpoint inhibition with HIV-specific therapeutic vaccination, reminiscent of what currently applied in oncologic protocols. We suggest that such an innovative strategy could permit drug-sparing regimens and, perhaps, lead to eradication of the infection in some patients.https://www.frontiersin.org/article/10.3389/fimmu.2018.02447/fullHIVTregimmune checkpointsHIV vaccinePD1 |
| spellingShingle | Gilberto Filaci Gilberto Filaci Daniela Fenoglio Daniela Fenoglio Lucia Taramasso Francesco Indiveri Antonio Di Biagio Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV Frontiers in Immunology HIV Treg immune checkpoints HIV vaccine PD1 |
| title | Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV |
| title_full | Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV |
| title_fullStr | Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV |
| title_full_unstemmed | Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV |
| title_short | Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV |
| title_sort | rationale for an association between pd1 checkpoint inhibition and therapeutic vaccination against hiv |
| topic | HIV Treg immune checkpoints HIV vaccine PD1 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02447/full |
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